Pediatric Review

International Journal of Obesity (2013) 37, 1–15; doi:10.1038/ijo.2012.144; published online 28 August 2012

Pharmacotherapy for childhood obesity: present and future prospects

R Sherafat-Kazemzadeh1, S Z Yanovski1,2 and J A Yanovski1

  1. 1Section on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
  2. 2Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

Correspondence: Dr JA Yanovski, Section on Growth and Obesity, program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Hatfield Clinical Research Center, Room 1E-3330, MSC 1103, Bethesda, MD 20892-1103, USA. E-mail:

Received 4 April 2012; Revised 31 July 2012; Accepted 31 July 2012
Advance online publication 28 August 2012



Pediatric obesity is a serious medical condition associated with significant comorbidities during childhood and adulthood. Lifestyle modifications are essential for treating children with obesity, yet many have insufficient response to improve health with behavioral approaches alone. This review summarizes the relatively sparse data on pharmacotherapy for pediatric obesity and presents information on obesity medications in development. Most previously studied medications demonstrated, at best, modest effects on body weight and obesity-related conditions. It is to be hoped that the future will bring new drugs targeting specific obesity phenotypes that will allow clinicians to use etiology-specific, and therefore more effective, anti-obesity therapies.


clinical trials; obesity drug therapy; anti-obesity agents; child; adolescent; review



Prevalence of pediatric obesity and its complications: implications for intervention

Childhood obesity (defined as body mass index (BMI) greater than or equal to95th percentile for age and sex standards by the US Centers for Disease Control) has increased alarmingly over the past four decades, with almost 17% of US children and adolescents considered obese.1 Globally, obesity is considered one of the leading risk factors contributing to morbidity and mortality.2 Although there is some evidence that childhood obesity prevalence rates in the United States,1, 3 Australia, China and some European countries4, 5, 6, 7, 8 may have stabilized, they remain unacceptably high.2, 9, 10, 11 Childhood obesity is not only associated with a higher risk of morbidity and premature death in adults, but is also accompanied by many comorbid medical conditions during childhood.12, 13, 14, 15, 16, 17, 18 The weight-related complications that arise during childhood, added to the risks for morbidity and mortality imparted to adults who were obese as children,19, 20, 21 make development of effective treatments imperative.

Role of lifestyle modification interventions in the treatment of pediatric obesity

Lifestyle modification interventions, including behavioral treatment, diet modification and physical activity, are the cornerstones of primary and secondary prevention/treatment of pediatric obesity.22 Some studies have shown long-lived effects on pediatric overweight23 specially from family-based or other behavioral treatments24 without adverse effects on growth and development.25 A Cochrane review and meta-analysis suggested some efficacy for such lifestyle modifications after 12 months of treatment with a BMI s.d. score change of −0.04 and −0.14, respectively, for children below and over 12 years of age.24 For young children (5–12 years old), a considerable effect size of 0.89 (reduction in percentage of overweight) has been reported.26, 27 However, such interventions have shown relatively limited success among severely obese children and adolescents in either reduction of body weight or improvement of medical outcomes.22, 24, 28, 29 Altogether, success of such interventions is closely related to external factors such as more family involvement, greater socioeconomic status and better cultural adaptation, which may not be attainable in every circumstance.30, 31, 32 As a result, there is considerable interest in combining lifestyle modification with more intensive strategies, including pharmacotherapy, to ameliorate pediatric obesity.33


In this paper, we critically review the limited available data for the safety and efficacy of medications that have been studied for the treatment of obesity in children and adolescents, including drugs approved for pediatric obesity treatment, those used off-label for obesity as well as drugs under development for treatment of obesity in adults (Table 1).

Data synthesis

A PubMed search was conducted with no limitation for year of publication to find reports investigating antiobesity drugs, utilizing the keywords ‘children’ or ‘adolescents’, ‘obesity,’ ‘appetite’ or ‘satiety’, ‘drug’ or ‘pharmacotherapy’ and ‘clinical trial’ or ‘meta-analysis’. The primary search resulted in 1296 articles for which the titles and/or abstracts were examined to determine if they complied with the search criteria. Automated searches were supplemented by examination of expert recommendation reports and bibliographic references from included research studies, as well as searches for the names of medications approved by the Food and Drug Administration (FDA) for weight-loss treatment or known to be used off-label for weight loss. Although the emphasis of this review is primarily on outcomes available from placebo-controlled, double-blind, randomized clinical trials, if other data were not available, we also present the results of open-label studies, as well as case series that report weight reduction as a primary or secondary endpoint of the study. Included pediatric clinical trials are enumerated in Supplementary Table 1. This review summarizes study design and clinical results achieved with each drug, with a discussion of methodology including subject characteristics, type and duration of intervention and adverse effects.

A brief appraisal of treatment options that are currently under investigation in adults will also be presented, based on a search conducted using ‘obesity,’ ‘appetite or satiety’, ‘drug or pharmacotherapy’ and ‘clinical trial’ or ‘review’ that was supplemented by manual searches for current and new drugs for adults (Table 1).


Indications and considerations for pharmacotherapy in children

Expert committee recommendations for treatment of obesity in children suggest use of a staged, individualized approach34 with medication employed after comprehensive nonpharmacologic multidisciplinary lifestyle modification interventions have failed.35 There are no pediatric experimental data establishing how long nonpharmacologic interventions should be attempted before medication is prescribed; typically, a 6-month trial is used.34 As observed in adults,36 greater weight reduction has been reported among adolescents prescribed weight-loss medications who adhered to lifestyle interventions.37 There are no pediatric data suggesting that obesity pharmacotherapy can be effectively prescribed without an accompanying lifestyle modification program.

Some experts believe that obesity pharmacotherapy should be reserved for children and adolescents with high BMI who also demonstrate an obesity-related comorbidity such as dyslipidemia, hypertension, insulin resistance, fatty liver disease or obstructive sleep apnea.34, 38 The argument made is that the potential benefits are more likely to outweigh the potential risks of pharmacotherapy among those who already manifest complications of excess weight. Not all pediatric obesity drug treatment trials or published recommendations33, 39 have required presence of obesity-related comorbidities.35

When the USFDA approves a medication for a specific indication in adults, the lower age limit for approved use is generally set at 16 years.40 Such medications will be described in this review as approved for adults. At the present time, only one agent (orlistat) holds FDA approval to treat obesity among adolescents aged 12–16 years; no weight-loss medications are approved for use in children <12 years old.


Current pharmacotherapeutic options for obesity treatment

Drugs decreasing energy intake

Classical centrally acting anorexiant medications

The classical anorexiants act within the central nervous system to alter the release and reuptake of neurotransmitters long known to be implicated in appetite: norepinephrine, serotonin and dopamine.41 No weight-loss medication with these mechanisms of action is currently approved for pediatric use and no available data support their long-term (>1 year) safety or efficacy in pediatric populations.

(a) Appetite suppressants with primarily adrenergic effects: Phentermine,42 diethylpropion43 and mazindol44, 45, 46, 47 are anorexiants approved by the FDA for short-term use in adults that exert anorexiant effects primarily by increasing adrenergic tone.48 They decrease food intake and also increase resting energy expenditure.49 Phentermine and diethylpropion are chemically related to amphetamines.50 Phentermine, mazindol and diethylpropion are Drug Enforcement Administration (DEA) schedule IV controlled substances, indicating a relatively low potential for abuse.51 Mazindol is not currently available in the United States, and phenylpropanolamine52 has been withdrawn because of increased risk of hemorrhagic stroke.53 Other drugs such as benzphetamine and phendimetrazine are also approved for short-term use with caution because of the potential risks such as pulmonary hypertension and valvular disease.54, 55 Only small pediatric trials using phentermine42, 56 or diethylpropion43, 57 that lasted no more than 12 weeks have been reported. The adverse effect profiles of phentermine and diethylpropion in adults include insomnia, restlessness and euphoria, palpitations, hypertension and cardiac arrhythmias, dizziness, blurred vision and ocular irritation. Because of the lack of long-term pediatric treatment trials showing safety and efficacy, these drugs are not recommended as weight loss medications in youth.

(b) Appetite suppressants with primarily serotonergic effects: There are several drugs for which pediatric trials exist that affect appetite primarily by increasing serotonergic release or inhibiting reuptake,48, 50 including fluoxetine, chlorphentermine, fenfluramine and its stereoisomer, dexfenfluramine.58, 59, 60, 61, 62, 63 None of these drugs are currently FDA-approved for weight loss and most have been removed from the US market. The longest pediatric trial studied fenfluramine versus placebo for 12 months in Brazilian adolescents.61 Among those completing the study, fenfluramine-treated adolescents reportedly decreased BMI by −5.1kgm−2 (placebo treated: −1.3kgm−2, P<0.05). Fenfluramine and dexfenfluramine were withdrawn in 1997, when cardiac valvulopathies similar to those seen in the carcinoid syndrome were found after their use.64, 65 Serotonergic anorexiant agents were also associated with an increased incidence of primary pulmonary hypertension.66 Other adverse effects of these agents included headache, abdominal pain, drowsiness, insomnia, dry mouth, increased activity and irritability.67

(c) Agents with primarily dopaminergic effects: Amphetamines, including methylphenidate and dextroamphetamine (DEA Schedule II controlled substances), increase dopaminergic tone by inhibiting dopamine reuptake57, 69. Acute studies demonstrate their ability to suppress appetite in obese adults,69 and anorexia is a frequently observed side effect when such medications are used in pediatric patients with attention deficit disorder.70, 71 Because of their adverse effect profile (agitation, insomnia, tachycardia, hypertension and hyperhidrosis), abuse potential72 and the absence of trials showing long-term weight-loss efficacy, these agents are not recommended or approved for obesity management.

(d) Agents with action at multiple monoamine receptors: Sibutramine, which inhibits norepinephrine and serotonin reuptake, was FDA approved in 1997 for weight loss and maintenance of weight loss in adults with a BMI greater than or equal to30 or greater than or equal to27kgm−2 with comorbidities.73 Adverse effects included increases in pulse and blood pressure. Sibutramine was voluntarily withdrawn from use in 2010 when a greater incidence of cardiovascular events was found among adults at high risk for cardiovascular disease who took the drug.

Sibutramine was never approved for use in children <16 years of age,74, 75 but it is one of the best-studied weight-loss medication in adolescents. Ten reports37, 76, 77, 78, 79, 80, 81, 82, 83, 84 from eight randomized controlled trials37, 76, 78, 79, 81, 82, 83, 84 and two open-label studies77, 80 investigated the efficacy of sibutramine for weight loss in obese adolescents. Sibutramine 5–15mgday−1 was administered as an adjunct to behavioral therapy with or without dietary intervention for 6- to 12-month periods and led to −2.9 to −3.6kgm−2 decreases in BMI. The largest trial was conducted on 498 obese adolescents randomized 3:1 to receive either sibutramine or placebo, in addition to caloric restriction and behavioral therapy for 12 months.78, 82 Sibutramine was initiated at 10mgday−1 and was increased to 15mgday−1 in the 48% of subjects who showed <10% BMI reduction. This 1-year therapy resulted in a 2.9kgm−2 BMI reduction in the sibutramine group (versus 0.3kg m−2 for placebo). Among those receiving sibutramine plus behavioral therapy, 62.3% achieved a >5% BMI reduction, versus 38.8% for placebo plus behavioral therapy. Treatment with sibutramine was associated with greater improvements in waist circumference, triglycerides, high-density lipoprotein cholesterol, insulin levels and insulin sensitivity. The effect of sibutramine on adolescent cardiovascular health was a matter of concern when the first pediatric data became available.85 Greater reductions in cardiovascular variables, including change in systolic and diastolic blood pressure, and pulse rate were generally seen in placebo-treated adolescents despite the greater weight loss in the sibutramine-treated groups. Statistically significant differences favoring placebo were found for systolic blood pressure,37 diastolic blood pressure78, 84 and heart rate.37, 78 Adult studies confirmed sibutramine increases blood pressure and heart rate.86, 87 In September 2010, SCOUT (Sibutramine Cardiovascular Outcomes Trial), a multinational, randomized, placebo-controlled trial conducted in 16 countries, with a mean of 3.4 years of duration designed to assess clinical outcome in subjects with high risk of cardiovascular events,88 found that rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively. The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group.88 These findings resulted in an FDA request to withdraw sibutramine from the US market.89 Apart from cardiovascular outcomes, other adverse effects included dry mouth, insomnia, constipation, headache and cholelithiasis. Sibutramine was contraindicated in individuals with pre-existing psychiatric disorders.74 Other contraindications included concurrent use of monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.90

Drugs in development or used off-label that may act centrally as anorexiant medications

Emerging knowledge of the physiologic processes that control food intake over the past 15 years has led to a greater understanding of both short-term signals that are involved in meal initiation and termination and longer-term regulators of energy balance. The adipocyte-derived hormone leptin91 conveys information about the status of adipocyte triglyceride content, as well as the energy and macronutrient composition of recent intake, to brain regions that control energy intake.92, 93, 94 Low concentrations of circulating leptin have been found to produce defects in both satiation and satiety, leading to hyperphagia.95 In the presence of leptin deficiency, activity increases in hypothalamic appetite-regulating neurons that release orexigenic peptides, and decreases in neurons that release anorexigenic factors.96 Hormones and neurotransmitter systems involved in modulating the hypothalamic leptin signaling pathway have therefore been investigated for their potential ability to alter body weight in obese individuals.

(a) Leptin: The discovery of leptin was received with great anticipation as a potential antiobesity therapy because of its ability to reverse excess adiposity in rodent models characterized by leptin deficiency.97, 98, 99 Indeed, leptin dramatically reduces body fat, suppresses appetitive behaviors and improves other leptin-responsive endocrine and metabolic abnormalities in children and adults with congenital leptin deficiency.100, 101, 102, 103 Open-label trials in pediatric and adult patients with leptin insufficiency due to congenital lipodystrophies also demonstrated long-term improvements in metabolism,104 as did placebo-controlled trials in leptin-insufficient women with hypothalamic amenorrhea.105 However, studies carried out in nonleptin-deficient adults have found relatively small effects on body weight, which limits leptin’s usefulness as a stand-alone antiobesity medication in those without leptin insufficiency.106, 107 In adults who have undergone substantial weight reduction, there is suggestive evidence that leptin treatment to restore serum leptin concentrations to preweight loss values may reverse the subtle muscular, neuroendocrine and autonomic adaptations to the weight-reduced state that may predispose such individuals to regain their lost weight.108, 109, 110, 111, 112 No trials have assessed leptin’s effects in nonleptin-deficient children during weight reduction or in the weight-reduced state.

(b) Bupropion: Bupropion113 is an antidepressant that inhibits presynaptic reuptake of both norepinephrine and dopamine. It is structurally close to the appetite suppressant diethylpropion.114 Pooled data meta-analysis of five studies among adults reported a pooled random-effect estimate of total weight loss of 4.44kg for Bupropion-treated adults as compared with 2.77kg for placebo at a mixed end point of 6 to 12 months;115 similar mean weight reduction was reported in a review of trials on patients with major depression.116 No pediatric randomized controlled trials of bupropion examining its effects on body weight have been published, although some short-term open-label studies suggest its use may be associated with small amounts of weight loss in adolescents.117, 118

(c) Lorcaserin: Lorcaserin is a selective 5-HT2C receptor agonist that acts primarily in the central nervous system to inhibit feeding behavior.119 In adults, a 3182-person phase III multicenter clinical trial (BLOOM) showed that 47.5% of those treated with lorcaserin, versus 20.3% of those given placebo, lost greater than or equal to5% of baseline body weight after 1 year; the average weight loss was 5.8kg for lorcaserin versus 2.2kg for placebo.120 A second trial (BLOSSOM)121 found similar efficacy among 4008 patients. Adult patients with type 2 diabetes also decreased weight after treatment.122 No pediatric trials have been reported. The common adverse events in both trials included headache, nausea and dizziness. The FDA approved lorcaserin, 10mg b.i.d., in June 2012 to treat adults with BMI greater than or equal to30 or greater than or equal to27kgm−2accompanied with at least one comorbid condition such as hypertension, type 2 diabetes mellitus or dyslipidemia.123, 124 Although lorcaserin use was not associated with valvular diseases in its placebo-controlled trials, it was recommended to be used with caution in patients with congestive heart failure. The company was required by the FDA to conduct long-term cardiovascular outcomes trial.123, 124 The package insert specifies that patients who have not lost greater than or equal to5% of baseline body weight by 12 weeks should discontinue lorcaserin.

(d) Tesofensine: Tesofensine is a triple monoamine reuptake inhibitor, blocking the presynaptic uptake of noradrenaline, dopamine and serotonin. A 24-week phase II trial of 203 adults reported weight losses of up to 10% of body weight (versus 2% in placebo) in tesofensine-treated adults.125 Body weight decreased 2.2kg in the placebo group and decreased 6.7–12.8kg with different dosages of tesofensine.125 Tesofensine increases satiety and may increase energy expenditure.126, 127 No pediatric studies have been reported.

(e) Cannabinoid (CB) receptor inhibitors: Stimulation of central CB1 receptors increases appetite and fat deposition. Clinical trials of rimonabant, a selective endocannabinoid (CB1 receptor) antagonist, indicated beneficial effects on weight, waist circumference, serum lipids, C-reactive protein and glycemic control in adult patients with type 2 diabetes.128, 129 The major adverse effects of rimonabant included nausea, anxiety and depression.130 The FDA did not approve rimonabant in 2007 because of concerns about neuropsychiatric adverse effects, particularly an increase in suicidality. Approved as a weight-loss medication in Europe in 2006, rimonabant was withdrawn by the European Medicines Agency in 2009 because of an increase in psychiatric adverse effects.131 Clinical development of rimonabant as well as other centrally acting CB1 inhibitors such as taranabant and otenabant was suspended as a result of this adverse event profile.73, 132, 133 More recent findings on CB1 receptor antagonism in the liver, adipocytes, muscle and pancreas have raised hopes for potentially new generation of peripherally acting CB1 receptor inhibitors for treatment of obesity and its comorbid conditions such as fatty liver, insulin resistance and dyslipidemia.134, 135, 136, 137

(f) Topiramate: Topiramate is a GABA-ergic anticonvulsant drug that was fortuitously found to induce weight loss in patients with epilepsy. Among obese adults, data from trials suggested the possibility of substantial weight loss (4.5 to 16.36kg for topiramate versus 1.7 to 8.6kg for placebo).138 Topiramate could also abrogate antipsychotic-induced weight gain.139 Common adverse events include paresthesias, taste impairment and psychomotor disturbances including difficulties with concentration and sedation. In children, topiramate has been studied for the treatment of epilepsy140 and migraine,141 where its use is associated with 1–2kg decreases in body weight versus placebo. A limited number of open-label case series142, 143, 144 have suggested potential improvements in body weight among children with antipsychotic-associated weight gain and in two extremely obese adolescent boys with Duchenne Muscular Dystrophy.145 Concerns over the impairment of cognitive function at dosages similar to those used to treat seizure disorders will likely limit its use as a stand-alone agent;146 no controlled trials restricted to obese children or adolescents have been reported. It is also important to note that there is concern that the risk for cleft lip with or without cleft palate is increased in children born to mothers who used topiramate during pregnancy.147, 148

(g) Amylin: Amylin is a pancreatic β-cell hormone that reduces food intake, slows gastric emptying and reduces postprandial glucagon secretion in humans. Many of its hypophagic actions in rodents appear dependent on direct activation of noradrenergic neurons within the area postrema.149 Amylin receptors in hind brain are hetero-oligomers with calcitonin receptors;150 amylin interacts with other signals involved in the short-term control of food intake, including cholecystokinin, glucagon-like peptide 1 (GLP-1) and peptide YY, and has been shown to decrease expression of orexigenic neuropeptides in the lateral hypothalamus.149 Pramlintide, a synthetic analog of amylin, is approved for the treatment of both type 1 and type 2 diabetes and produces small weight losses in obese and diabetic adults.151, 152 One study of adults with and without type 2 diabetes found a placebo-subtracted weight loss of up to 2.7kg after 16 weeks of thrice-daily high-dose (240μg) pramlintide.153 In another study among 411 obese subjects, mean weight loss after 4 months for placebo was 2.8±0.8kg, whereas for different pramlintide dosages it ranged between 3.8±0.7 and 6.1±0.7kg.154 The main adverse effects are nausea and abdominal discomfort. Although small trials of pramlintide have been reported in adolescents with type 1 diabetes,155, 156 no pediatric or adolescent weight loss studies have been conducted.

(h) Gut-derived hormones: (1) Ghrelin. Ghrelin, produced by gastric enteroendocrine cells, is a circulating orexigenic hormone with marked fluctuations around meals. Short-term human studies find that ghrelin infusions increase food intake.157 The importance of hyperghrelinemia as a cause of obesity and the efficacy of inhibition of ghrelin action for obesity treatment are uncertain, as ghrelin concentrations are usually suppressed by obesity. Obese patients with the Prader–Willi syndrome (PWS) display unusually high circulating concentrations of ghrelin,158 but treatment with octreotide (which suppresses ghrelin production) does not induce weight loss or reduce hyperphagia among these patients.159

(2) Incretin hormones. Incretin hormones, including GLP-1, so named because they enhance glucose-stimulated insulin secretion, exert central anorectic effects in addition to their peripheral actions. Exenatide and liraglutide (GLP-1 analogs) are approved by FDA for adjunct treatment of type 2 diabetes mellitus in adults. Astrup et al.160 reported a dose-dependent mean weight loss of 4.8–7.2kg with liraglutide as compared with 2.8kg with placebo after 20 weeks in obese individuals without type 2 diabetes. Others, however, reported somewhat smaller effect sizes in trials lasting up to 2 years.161, 162, 163, 164, 165, 166 In nondiabetic subjects, placebo-controlled trials lasting up to 24 weeks found a 5.1-kg weight reduction for exenatide versus 1.6kg for placebo.167 One 12-week crossover study of 12 extremely obese children has reported a treatment effect of −3.9kg compared with behavioral intervention alone from exenatide.168 Studies documenting the long-term safety, tolerability and efficacy of GLP-1 analogs in children and adolescents are needed.

Drugs affecting nutrient trafficking

Medications affecting digestion in the gut

(a) Orlistat: By inhibiting gastrointestinal lipases, orlistat reduces the absorption of ~30% of ingested dietary fat. Orlistat 120mg three times a day was approved by the FDA in 2003 for management of obesity in adolescents 12–16 years of age.169 The trials conducted to examine the efficacy of orlistat among adolescents lasted from 21 days to 15 months.170, 171, 172, 173, 174, 175, 176 The largest study randomized 539 adolescents 12–16 years old for 52 weeks 3:1 to orlistat or placebo, with both groups receiving a multivitamin, instructions to follow a hypocaloric diet and a physical activity prescription. Approximately 35% withdrew from each group. In both arms, BMI decreased until week 12, then stabilized in the orlistat group but increased with placebo. There was an overall −0.55kgm−2 decrease in BMI with orlistat versus a +0.31kgm−2 increase with placebo after 52 weeks (P<0.001). The most common adverse events were oily stools (50%), oily spotting (29%), oily evacuation (23%), abdominal pain (22%) and fecal urgency (21%). Seven participants on orlistat therapy and one child in the placebo group developed gallstones. However, only 2% of the dropouts in the orlistat group were described as due to drug-related adverse effects.175 A secondary analysis of the same study indicated that response to treatment after 12 weeks was highly correlated with the amount of weight lost at the study end point (52 weeks),177 suggesting that early weight loss with orlistat is a strong predictor of long-term success with the compound. Another large 6-month randomized placebo-controlled study of 200 African-American and Caucasian severely obese adolescents with obesity-related comorbid conditions published in an abstract form178 enrolled participants in a 12-week intensive weight reduction program with a 1:1 randomization to orlistat or placebo. Those taking orlistat lost 2.9kg compared with 0.6kg weight reduction in the placebo group, but had no significant improvements in their comorbid conditions. Small but significant increases in serum liver enzyme concentrations were also found in orlistat-treated subjects. Orlistat has undergone two label changes because of reports of liver injury, cholelithiasis and pancreatitis; however, a cause-and-effect relationship of severe liver injury with orlistat use has not been established.169 There is one report of acute hepatic injury in a 15-year old girl, which resolved after the medication was stopped.179 As a lower dose (60mg) of orlistat was approved as an over-the-counter medication for adults in 2007, accidental ingestion has been reported in children below age 5 years. Data on exposures are limited, but among 45 patients with reported outcomes, there were no cases of severe, persistent effects.180 Ingestion of dosages as high as 5g have been described with no serious adverse events identified.181 Although adult patients have experienced improvements in glucose and insulin levels while taking orlistat,182 metabolic benefits from orlistat therapy among adolescents have been reported only in a 20-person, 6-month, open-label study by McDuffie et al.174, 183 (a reduction in total cholesterol, low-density lipoprotein cholesterol, fasting glucose and insulin) and Chanoine et al.175 (a decrease of −0.51mmHg vs an increase of +1.30mmHg for diastolic blood pressure in orlistat vs placebo over 12 months). Because orlistat leads to decreased absorption of fat-soluble vitamins,183 supplementation with a daily multivitamin is recommended.184 The withdrawal rates among trials range from 0 to 35%. Orlistat should not be prescribed to patients with cholestasis or chronic malabsorption.

Orlistat produces modest weight loss and its long-term efficacy for adolescents has not been established beyond 1 year. The thrice-daily recommended dosing is another significant limitation to the wide use of this drug among adolescents. Although orlistat is the only FDA-approved treatment for obesity among adolescents under the age of 16 years, it appears to offers little prospect of benefit to those with severe obesity.

(b) Cetilistat: Cetilistat is a gastrointestinal lipase inhibitor currently under investigation.185, 186 A multicenter study of 612 adults found similar weight reductions for cetilistat and orlistat over 12 weeks among obese adults with type 2 diabetes treated with metformin, but with somewhat fewer adverse gastrointestinal events for cetilistat.187 As weight reductions were no greater than for orlistat, it can be anticipated that cetilistat will prove of similar modest utility for weight reduction.

(c) Acarbose: Acarbose is a pseudotetrasaccharide that competitively inhibits intestinal α-glucosidase in the intestinal brush border.188 This compromises the uptake of monosaccharides, leading to lower postprandial insulin and glucose.188 Acarbose is approved for diabetes treatment, where it produces small weight losses in some studies among adults (0.46kg weight loss vs 0.33kg weight gain with placebo).189, 190, 191 There have been no published pediatric trials for acarbose as an antiobesity drug, and given its meager efficacy in adults, it appears unlikely that acarbose will be developed for weight control.

Medications affecting renal nutrient reabsorption

Dapagliflozin and Sergliflozin193, 194 are investigational selective inhibitors of the sodium-dependent glucose cotransporter-2 in the renal tubule. They suppress renal glucose reabsorption, resulting in a dose-related glucosuria.194 These drugs were developed to improve glycemic control in type 2 diabetic patients, also also induce weight loss. Among patients with type 2 diabetes, when compared with placebo, dapagliflozin induced significant improvements in glycemic control and reductions in body weight ranging from 2–5 to kg195, 196, 197, 198 (vs 0.95–1.55kg reductions for placebo) because of the ~70gday−1 glucose that is excreted rather than reabsorbed in those given dapagliflozin.194 The side effects include urinary tract and genital infections, volume depletion leading to increases in hematocrit and blood urea nitrogen and hypoglycemia in those with diabetes. In July 2011, the FDA advisory committee voted against approval of dapagliflozin for treatment of type 2 diabetes, mainly because of concerns over liver damage and a link to bladder and breast cancer.199 No trials in obese, nondiabetic individuals have as yet been reported for these agents.

Drugs affecting metabolism

Modulation of insulin action

(a) Metformin: Metformin is a biguanide that inhibits intestinal glucose absorption, reduces hepatic glucose production and increases insulin sensitivity in peripheral insulin-targeted tissues.200, 201 Metformin is approved for the treatment of type 2 diabetes in adults and children over age 10 years,202 but is not approved for treatment of obesity. Its administration has been associated with modest weight loss and reduction of insulin resistance among nondiabetic adults200 as well as prevention or delay of type 2 diabetes onset.203 Studies on the effects of metformin as a weight-loss treatment among adolescents are few and most are short-term trials (≤6 months).205, 206 The study with longest placebo-controlled duration randomized adolescents to 48 weeks of daily metformin hydrochloride extended-release therapy or placebo in the context of a lifestyle intervention program. For this multicenter, randomized, double-blind, placebo-controlled trial, 92 obese adolescents completed a single-blind placebo 4-week run-in phase, after which the 77 subjects who demonstrated 80% medication compliance and attended at least 2 of the 3 scheduled lifestyle modification sessions, were randomized.206 The BMI change among those who completed the trial was significantly different: −0.9kgm−2 in the metformin group versus +2.2kgm−2 in the placebo arm, but metformin treatment did not produce a significant change in total fat mass, abdominal fat or insulin. The largest randomized controlled trial in younger children207 randomized 100 severely obese, insulin-resistant children aged 6–12 years to metformin or placebo for 6 months, followed by another 6 months of open-label metformin treatment. In 17% of subjects, the maximum dosage of 2000, mgday−1 was not tolerated and had to be reduced. In an intent-to-treat analysis of those who finished the placebo-controlled phase (85% in each group), the average weight change in the metformin group was +1.47kg versus +4.85 in the placebo group.207 Gastrointestinal complaints (liquid or loose stools and vomiting) were significantly more prevalent among those treated with metformin, yet only two participants were reported as leaving the study because of medication intolerance. Fatigue was also significantly more likely to be reported among the metformin-treated children.

The metabolic effects of metformin in nondiabetic children and adolescents are inconsistent among studies.206, 207, 208, 209, 210 In the available controlled trials, metformin’s effect on BMI in children and adolescents varies, ranging from no change211 to −0.5 to −1.5kgm−2. Metformin has also been studied in the context of treatment of the polycystic ovary syndrome among adolescent girls, with observed reductions in BMI ranging from 0 to 3kgm−2.212, 213, 214, 215, 216, 217, 218 A placebo-controlled trial involving 38 adolescents with >10% weight gain on psychotropic drugs has also reported weight stabilization on metformin (mean weight change −0.13±2.88kg) while subjects receiving placebo continued to gain weight (+4.01±6.23kg) over 16 weeks.219 Pooling the results of the two available studies of metformin as an agent for weight control among subjects receiving antipsychotic drugs suggests ~4.1% reduction in body weight.220 In sum, it appears that metformin has relatively modest, but significant, effects on body weight in obese children and adolescents, similar to its effects in adults. The main adverse effects of metformin are diarrhea, nausea, vomiting and flatulence, which are usually transient and mild to moderate. The odds ratio of having biochemical Vitamin B12 deficiency is reported to be 2.92 in diabetic patients on metformin treatment based on data from the National Health and Nutrition Examination Survey (NHANES), 1999–2006,221 yet there is no official recommendation for supplementation among these patients. Metformin is contraindicated in renal failure, should be withheld in critically ill patients and when use of imaging contrast agents is anticipated. Given its chemical similarity to phenformin, concerns were raised that metformin might predispose patients to the development of lactic acidosis; however, a recent meta-analysis in Cochrane reviews reported no evidence supporting such a relationship.222 With its modest impact on weight, metformin does not appear particularly efficacious for weight reduction. Its ability to prevent or delay the onset of dysglycemia in children remains unproven and requires further study.

(b) Octreotide: Octreotide is a somatostatin analog that, among its manifold effects, inhibits glucose-dependent insulin secretion from pancreatic β-cells.223 There are three studies evaluating this drug for weight loss via subcutaneous injection in pediatric patients with hypothalamic obesity, who are believed to have elevated insulin production, perhaps in response to the stimulation of hepatic glucose production that results from their hypothalamic damage. These trials demonstrated either small weight losses or reduced weight gain in octreotide-treated subjects. One study159 has examined the effect of octreotide on patients with PWS because of its ability to suppress ghrelin. After 16 weeks of monthly octreotide administration, there was no significant change in BMI compared with placebo.159 The major adverse effect from octreotide is development of cholelithiasis or biliary sludging in up to 44% of subjects. Transient elevation of blood glucose (15–27%), diarrhea (36–48%), abdominal pain or discomfort, flatulence, influenza-like symptoms, constipation, headache, anemia, hypertension, dizziness, fatigue, nausea and vomiting also occur.159, 224 Octreotide cannot be recommended for treatment of obesity outside of clinical trials.

Modulation of lipolysis

Growth hormone (GH) inhibits lipoprotein lipase, increases hormone-sensitive lipase and stimulates adipocyte lipolysis.225 GH also stimulates protein synthesis and increases fat-free mass (both muscle and bone mass). Studies in GH-deficient adults and children confirm that fat mass decreases after GH treatment.226, 227, 228, 229 Treatment with recombinant human GH is FDA approved for children with PWS to increase height velocity.74 A decrease in fat mass and an increase in lean body mass are observed among both adult and pediatric patients with PWS who are given GH.230, 231, 232 There is, however, no indication to use recombinant human GH for nonsyndromic obesity in the absence of GH deficiency. A review of clinical trials of GH administration in patients with obesity showed no better performance for recombinant human GH than for a hypocaloric diet.233 Tumor development especially among patients who previously received irradiation for treatment of intracranial malignancies and potential adrenal insufficiency in previously unidentified hypopituitary patients are among the concerns with recombinant human GH treatment.234 Changes in glucose metabolism may appear during long-term treatment with GH in PWS that necessitates glucose monitoring among these patients.235 There are also concerns about GH causing greater cardiac diameters in PWS patients, although short-term studies do not support this finding.236 Similarly, there are contradictory reports on the effect of GH treatment on respiratory symptoms (specifically sleep apnea) among PWS patients.237, 238 Currently, the FDA has added labeling to GH products stating that GH therapy is contraindicated in patients with PWS who are severely obese or have severe respiratory impairment239 because there may be an increased risk of sudden death.240

Modulation of energy expenditure

There are currently no medications augmenting energy expenditure that are approved for clinical use in the treatment of obesity. Thermogenic agents are appealing in theory, but have been found either to be ineffective or, when effective, to have unacceptable adverse consequences.241

(a) Thyroid hormones: Thyroid hormones can increase energy expenditure, but only when doses sufficient to cause hyperthyroidism are given.242 Thus, thyroid hormone treatments are not recommended for weight loss in children or adults.243 The thyroid hormone receptor-β1-selective thyromimetics with a safer profile with regard to cardiac and skeletal effects while exerting favorable effects on plasma cholesterol and triglyceride levels are under development.244 So far, early phases of clinical trials have not shown much efficacy for weight loss.245

(b) β3-Adrenergic receptor agonists: The β3-adrenergic receptor activation by β-agonists induces lipolysis and increases fatty acid oxidation and induces weight loss in rodent obesity models. Unfortunately, human trials have not found significant weight losses or effects on energy expenditure from such agents.246, 247, 248

(c) Caffeine plus ephedrine: Ephedrine, a drug enhancing catecholaminergic tone that previously was available without a prescription, was withdrawn in 2002 by the FDA because of cardiovascular risks. The thermogenic effects of ephedrine in humans are greatly increased when methylxanthines such as caffeine, which inhibit phosphodiesterases, are coadministered.249 In adults, an herbal caffeine/ephedrine preparation produced a weight reduction of 5.3 versus 2.6kg with placebo;250 larger weight reductions were reported in a case series of three patients with hypothalamic obesity.251 One small study, which randomized 16 adolescents to caffeine plus ephedrine and 16 to placebo, reported significant weight loss (2.9kgm−2 vs 0.5kgm−2 with placebo) in a 5-month trial.252 The side effects included nausea, insomnia, tremor, dizziness and palpitations.253 Other studies among adults usually had small sample sizes, and the results were not consistent.254, 255, 256, 257, 258, 259, 260

New combination therapies

As body weight is defended by multiple, redundant neural mechanisms, it is reasonable to attempt obesity treatment by targeting multiple weight-regulating pathways at the same time. The most successful of these combinations in adults was fenfluramine plus phentermine, for which weight losses were demonstrated in a cohort of 52 obese adults followed for 190 weeks.261, 262 The efficacy of fenfluramine plus phentermine provided proof of principle that combination therapy might be useful, even though fenfluramine’s adverse cardiac toxicity led to its withdrawal from clinical use.

(I) Phentermine plus topiramate: When low-dose, controlled-release phentermine was combined with the glutamatergic and GABA-ergic antiepileptic topiramate in a large phase III study (more than 1400 participants on treatment arms with different doses), the subjects lost 10.2kg on combination therapy versus 1.4kg with placebo over 56 weeks.263 The most common adverse events were dry mouth paresthesias, constipation, insomnia, dizziness and dysgeusia. Depression- and anxiety-related adverse events were also observed. The medication had favorable effects on glycemia, including progression to diabetes, improvements in lipids, blood pressure, sleep apnea and quality-of-life measures. There was also, as previously noted, a small but consistent increase in pulse rate.148 However, medication use for obesity-related comorbid conditions was reduced in the treatment groups compared with placebo. The overall rate of adverse effects decreased in weeks 56–108 compared with weeks 0–56; among which dry mouth, constipation and paresthesias were the most prevalent.264, 265, 266 There were 19 pregnancies carried to term during these studies, none of which resulted in congenital abnormalities.148 In July 2012, the FDA voted for approval of phentermine (3.75–15mgday−1) plus extended-release topiramate (23–92mgday−1) as an adjunct to diet and physical activity for treatment of obesity among adult individuals with BMI greater than or equal to30 or greater than or equal to27kgm−2 with at least one obesity-related comorbid condition.267 The drug will carry a warning of potential increased risk for orofacial clefts in neonates exposed to topiramate during the first trimester of gestation and will be subject to a Risk Evaluation and Mitigation Strategy (REMS) that will restrict prescribing to trained clinicians, will require effective contraception and monthly pregnancy tests for reproductive-age women and will restrict dispensing to specific mail-order pharmacies. The company is also required to carry a long-term cardiovascular outcomes trial.267 No randomized pediatric studies have as yet been reported.

(II) Bupropion plus zonisamide: Administration of Bupropion and Zonisamide (an anticonvulsant medication with serotonergic and dopaminergic activity) was reported to produce a weight loss of 7.2kg versus 2.9kg with zonizamide alone among women in short-term phase II trials, with the most important adverse effects being headache, nausea and insomnia.73, 268 Phase II trial data collection ended in 2009; additional results of trials are not available in published form.

(III) Bupropion plus naltrexone: This proposed combination is based on the premise that naltrexone can block proopiomelanocortin neuron autoinhibition by endogenous opioids, whereas bupropion amplifies the anorexic α-melanocyte-stimulating hormone release.269 Combination therapy is more effective than placebo or bupropion monotherapy, with almost double the number of subjects losing >5% of their body weight compared with placebo.270, 271, 272, 273 In a modified-Intention-to-Treat Last-Observation-Carried-Forward analysis, the combination resulted in 9.3±0.4% weight loss compared with 5.1±0.6% for placebo.274 Nausea has been the most frequent adverse event, although there are also concerns about increases in blood pressure and risk for seizures from the use of bupropion.275 Overall, there was a 46% dropout rate (vs 45% in placebo group), among which 23% was because of adverse effects (12% in placebo group), suggesting tolerability issues.271 The FDA Endocrinologic and Metabolic Drugs Advisory Committee recommended approval of this combination drug as an antiobesity agent in December 2010,276 but also recommended additional investigations of its potential adverse effects. The FDA decided in February 2011 that an approval could not be granted until additional studies of long-term cardiovascular safety have been completed.277 The manufacturer announced in February 2012 its plan to conduct the cardiovascular outcome trial required by the FDA.278

(IV) Amylin plus leptin: A study of pramlintide plus metreleptin for 24 weeks showed a 12.7% weight loss from 24 weeks of combination therapy, a greater effect than monotherapy with either drug, with an overall weight change rate of −0.16 and −0.17kg per week for metreleptin and pramlintide, and −0.36kg per week for the combination of the two drugs.153, 279, 280 This combination requires injections, which may limit its extensive use. Nausea and injection site reactions were the main adverse effects.279

(V) Pramlintide plus phentermine or sibutramine: Based on preclinical studies on dietary-induced obese rats, which showed a reduction in food intake (up to 40%) and body weight (up to 12%) after administration of amylin together with either phentermine or sibutramine,281 the effect of these combinations have been tested among 244 nondiabetic subjects versus placebo in a 24-week, open-label trial.282 Weight loss with either combination was ~11kg, whereas pramlintide alone resulted in −3.6kg weight change. The main adverse effect was nausea among all groups receiving pramlintide;elevated diastolic blood pressure and heart rate were noted in the combination therapies.



Effective pharmacotherapy that reverses excessive adiposity and improves obesity-related comorbid conditions in pediatric patients remains elusive. The weight management impact of available drugs has been modest. Meta-analyses of trials for weight loss in pediatric samples have shown a meager effect size of −0.7kgm−2 for orlistat and a nonsignificant −0.17kgm−2 for metformin—no greater than the effect sizes found for behavioral interventions.22 Even when combined with state-of-the-art behavioral interventions, existing pharmacotherapy among adolescents has only moderate efficacy.31, 175, 206 Current guidelines, however, include medication in their recommended approaches to treat obese adolescents.34, 35

The most efficacious medications for treating obesity have, unfortunately, had to be withdrawn because of adverse events. Because of the importance of the metabolic pathways involved in the regulation of energy balance, it is unlikely that any highly effective weight-loss medication will be risk free. Careful evaluation is required to balance potential known and unknown adverse effects against the potential benefits of antiobesity medications in an individual child that may include improvements in metabolic, functional and patient-reported outcomes such as quality of life.

Because obesity is a chronic condition, pediatric obesity treatments should demonstrate long-term safety and tolerability, as well as efficacy. The long-term impact of medications that have central nervous system effects or that interfere with absorption of nutrients are particularly concerning when used in growing children and adolescents. Potential teratogencity of agents expected to be used in adolescent girls, in whom any pregnancy is likely to be unplanned, are also a particular concern. The bar for consideration of using obesity medications in children should be appropriately high, and commensurate with each medication’s potential benefits, safety profile and efficacy.

Why does pharmacotherapy for obesity fail so frequently due to either lack of efficacy or unacceptable adverse events or both? Obesity is a multifactorial, polygenic condition. There are myriad redundant pathways involved in detecting the body’s fuel abundance, adjusting energy requirements, regulating appetite and satiety and determining body weight set-point, set against the background of an obesity-promoting environment and individual psychosocial and cultural factors. Much remains to be discovered about the etiologic heterogeneity that can be anticipated to lead to disparities in the efficacy of medications among study participants. The value of using a specific treatment directed toward an established obesity-causing mechanism has already been shown for children and adolescents with one extremely rare form of monogenic obesity: leptin is remarkably successful to treat the obesity of leptin deficiency.101, 103 It seems likely, therefore, that once a more complete differential diagnosis for pediatric obesity can be established based on genetic (and perhaps epigenetic) and phenotypic characteristics, new drug trials can be initiated that select patients who are more likely to respond to a given medication.

The belief that most patients with significant obesity have multiple contributing genetic loci is supported by recent genomewide association studies.283, 284, 285 Many of the identified genotypes are associated with early obesity traits. Thus, for many, if not most children, targeted combination therapies that affect multiple impaired weight-regulating systems are likely to be required to improve body weight and avoid obesity’s comorbid conditions. The ability of combination drug therapy to ameliorate pediatric obesity safely remains to be demonstrated in meticulously designed clinical trials with adequate power. Dysregulation of other metabolic systems that have redundancy in their control mechanisms has been amenable to such an approach. For example, hypertension is now commonly treated with pharmacotherapeutic regimens that are directed against three or more different blood pressure control points.286

If novel single or combination therapies are to be tested in the future for their impact on pediatric obesity and its complications, the clinical trials would be most useful if they are conducted as randomized, placebo-controlled trials, have carefully justified subject selection criteria and outcomes, are adequately powered to account for potentially high attrition rates,22, 287 have long-term follow-up and are reported according to the CONSORT statement.288 Obesity is a chronic condition but most pediatric studies have a short duration (6 to 12 months); thus, there is little information available about the effectiveness and adverse effects from long-term use of obesity medications in children and adolescents. Appropriate short- and long-term outcomes need to be identified for pediatric populations, rather than necessarily using adult-oriented outcomes. Although a good case can be made for using change in BMI rather than change in BMI percentile or BMI s.d. score as the primary outcome in weight-loss studies among obese children and adolescents,289, 290 age-specific metrics are likely to be appropriate for metabolic and behavioral outcomes. Meta-analyses on clinical trials among adults show that there is usually little weight loss reported beyond the typical plateau at 6 months, which is followed by weight regain during the next few years.291, 292

Primary prevention and lifestyle intervention for those already overweight or obese are the foundations for weight management for children, adolescents and adults. For obese youth who are unable to achieve sufficient weight loss with lifestyle interventions alone, adjunctive use of more intensive treatments, including pharmacotherapy, may be appropriate. However, the search for obesity medications that are safe for long-term use, sufficiently efficacious to promote enough weight loss to improve health and have a favorable risk–benefit ratio remains elusive. Nevertheless, there is great hope that development of more effective, etiology-based antiobesity therapies for children and adults will prove possible.


Conflict of interest

RS-K and SZY declare no conflict of interest. JAY is a Commissioned Officer in the United States Public Health Service, Department of Health and Human Services. JAY was the principal investigator for NICHD-sponsored clinical studies using metformin, orlistat and betahistine, and has received orlistat and matching placebo from Roche Pharmaceuticals and betahistine and matching placebo plus research support for clinical research studies from Obecure.



  1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA 2012; 307: 483–490. | Article | PubMed |
  2. World Health Organization. Obesity and Overweight Fact sheet Number 311. Accessed: 25 November 2011.
  3. Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA 2010; 303: 242–249. | Article | PubMed | ISI | CAS |
  4. Rokholm B, Baker JL, Sorensen TI. The levelling off of the obesity epidemic since the year 1999 - a review of evidence and perspectives. Obes Rev 2010; 11: 835–846. | Article | PubMed | ISI | CAS |
  5. Sundblom E, Petzold M, Rasmussen F, Callmer E, Lissner L. Childhood overweight and obesity prevalences levelling off in Stockholm but socioeconomic differences persist. Int J Obes (Lond) 2008; 32: 1525–1530. | Article | PubMed | CAS |
  6. Salanave B, Peneau S, Rolland-Cachera MF, Hercberg S, Castetbon K. Stabilization of overweight prevalence in French children between 2000 and 2007. Int J Pediatr Obes 2009; 4: 66–72. | Article | PubMed | ISI |
  7. Peneau S, Salanave B, Maillard-Teyssier L, Rolland-Cachera MF, Vergnaud AC, Mejean C et al. Prevalence of overweight in 6- to 15-year-old children in central/western France from 1996 to 2006: trends toward stabilization. Int J Obes (Lond) 2009; 33: 401–407. | Article | PubMed | CAS |
  8. Olds T, Maher C, Zumin S, Peneau S, Lioret S, Castetbon K et al. Evidence that the prevalence of childhood overweight is plateauing: data from nine countries. Int J Pediatr Obes 2011; 6: 342–360. | Article | PubMed |
  9. Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006; 1: 11–25. | Article | PubMed | ISI |
  10. Kipping RR, Jago R, Lawlor DA. Obesity in children. Part 1: Epidemiology, measurement, risk factors, and screening. BMJ 2008; 337: a1824. | Article | PubMed |
  11. Mirmiran P, Sherafat-Kazemzadeh R, Jalali-Farahani S, Azizi F. Childhood obesity in the Middle East: a review. East Mediterr Health J 2010; 16: 1009–1017. | PubMed |
  12. August GP, Caprio S, Fennoy I, Freemark M, Kaufman FR, Lustig RH et al. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. J Clin Endocrinol Metab 2008; 93: 4576–4599. | Article | PubMed | ISI | CAS |
  13. Lee E. The world health organization's global strategy on diet, physical activity, and health: Turning strategy into action. Food Drug Law J 2005; 60: 569–601.
  14. Freedman DS, Kahn HS, Mei Z, Grummer-Strawn LM, Dietz WH, Srinivasan SR et al. Relation of body mass index and waist-to-height ratio to cardiovascular disease risk factors in children and adolescents: the Bogalusa Heart Study. Am J Clin Nutr 2007; 86: 33–40. | PubMed | ISI | CAS |
  15. Freedman DS, Katzmarzyk PT, Dietz WH, Srinivasan SR, Berenson GS. Relation of body mass index and skinfold thicknesses to cardiovascular disease risk factors in children: the Bogalusa Heart Study. Am J Clin Nutr 2009; 90: 210–216. | Article | PubMed | CAS |
  16. Young-Hyman D, Schlundt DG, Herman L, De Luca F, Counts D. Evaluation of the insulin resistance syndrome in 5- to 10-year-old overweight/obese African-American children. Diabetes Care 2001; 24: 1359–1364. | Article | PubMed | ISI | CAS |
  17. Csabi G, Torok K, Jeges S, Molnar D. Presence of metabolic cardiovascular syndrome in obese children. Eur J Pediatr 2000; 159: 91–94. | Article | PubMed | ISI | CAS |
  18. Daniels SR. Complications of obesity in children and adolescents. Int J Obes (Lond) 2009; 33 (Suppl 1): S60–S65. | Article | PubMed |
  19. Baker JL, Olsen LW, Sorensen TI. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 2007; 357: 2329–2337. | Article | PubMed | ISI | CAS |
  20. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011; 365: 1876–1885. | Article | PubMed | ISI | CAS |
  21. Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 1992; 327: 1350–1355. | Article | PubMed | ISI | CAS |
  22. McGovern L, Johnson JN, Paulo R, Hettinger A, Singhal V, Kamath C et al. Clinical review: treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials. J Clin Endocrinol Metab 2008; 93: 4600–4605. | Article | PubMed | ISI |
  23. Flynn MA, McNeil DA, Maloff B, Mutasingwa D, Wu M, Ford C et al. Reducing obesity and related chronic disease risk in children and youth: a synthesis of evidence with 'best practice' recommendations. Obes Rev 2006; 7 (Suppl 1): 7–66. | Article | PubMed | ISI |
  24. Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009. CD001872.
  25. Epstein LH, McCurley J, Valoski A, Wing RR. Growth in obese children treated for obesity. Am J Dis Child 1990; 144: 1360–1364. | PubMed | CAS |
  26. Young KM, Northern JJ, Lister KM, Drummond JA, O'Brien WH. A meta-analysis of family-behavioral weight-loss treatments for children. Clin Psychol Rev 2007; 27: 240–249. | Article | PubMed |
  27. Whitlock EP, O'Conner EA, Williams SB, Beil TL, Lutz KW Effectiveness of Primary Care Interventions for Weight Management in Children and Adolescents. An Updated, Targeted Systematic Review for the US Preventive Services Task Force. Agency for Healthcare Research and Quality (US); Report No.: 10-05144-EF-1. Evidence Synthesis, No. 76. January 2010.
  28. Fowler-Brown A, Kahwati LC. Prevention and treatment of overweight in children and adolescents. Am Fam Physician 2004; 69: 2591–2598. | PubMed |
  29. Kalarchian MA, Levine MD, Arslanian SA, Ewing LJ, Houck PR, Cheng Y et al. Family-based treatment of severe pediatric obesity: randomized, controlled trial. Pediatrics 2009; 124: 1060–1068. | Article | PubMed | ISI |
  30. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year outcomes of behavioral family-based treatment for childhood obesity. Health Psychol 1994; 13: 373–383. | Article | PubMed | ISI | CAS |
  31. Seo DC, Sa J. A meta-analysis of obesity interventions among U.S. minority children. J Adolesc Health 2010; 46: 309–323. | Article | PubMed | ISI |
  32. Epstein LH, Paluch RA, Roemmich JN, Beecher MD. Family-based obesity treatment, then and now: twenty-five years of pediatric obesity treatment. Health Psychol 2007; 26: 381–391. | Article | PubMed | ISI |
  33. Spear BA, Barlow SE, Ervin C, Ludwig DS, Saelens BE, Schetzina KE et al. Recommendations for treatment of child and adolescent overweight and obesity. Pediatrics 2007; 120 (Suppl 4): S254–S288. | Article | PubMed | ISI |
  34. Barlow SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007; 120 (Suppl 4): S164–S192. | Article | PubMed | ISI |
  35. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011; 128 (Suppl 5): S213–S256.
  36. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353: 2111–2120. | Article | PubMed | ISI | CAS |
  37. Berkowitz RI, Wadden TA, Tershakovec AM, Cronquist JL. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. JAMA 2003; 289: 1805–1812. | Article | PubMed | ISI | CAS |
  38. Yanovski JA. Intensive therapies for pediatric obesity. Pediatr Clin North Am 2001; 48: 1041–1053. | Article | PubMed | CAS |
  39. Daniels SR, Benuck I, Christakis DA, Dennison BA, Gidding SS, Gillman MW et alOverweight and Obesity. Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: The Report of the Expert Panel. NHLBI NIH Guidelines, NHLBI, DHHS: Bethesda, MD, 2011. pp 282–320.
  40. US Food and Drug Administration. Qualifying for Pediatric Exclusivity Under Section 505A of the Federal Food, Drug, and Cosmetic Act: Frequently Asked Questions on Pediatric Exclusivity (505A), The Pediatric ‘Rule,’ and their Interaction. Development & Approval Process (Drugs). Accessed: 30 March 2012.
  41. Samanin R, Garattini S. Neurochemical mechanism of action of anorectic drugs. Pharmacol Toxicol 1993; 73: 63–68. | Article | PubMed | CAS |
  42. von Spranger J. Phentermine resinate in obesity. Clinical trial of Mirapront in adipose children. Munch Med Wochenschr 1965; 107: 1833–1834. | PubMed |
  43. Andelman MB, Jones C, Nathan S. Treatment of obesity in underprivileged adolescents. Comparison of diethylpropion hydrochloride with placebo in a double-blind study. Clin Pediatr (Phila) 1967; 6: 327–330. | Article | PubMed |
  44. Dolecek R. Endocrine studies with mazindol in obese patients. Pharmatherapeutica 1980; 2: 309–316. | PubMed |
  45. Golebiowska M, Chlebna-Sokol D, Kobierska I, Konopinska A, Malek M, Mastalska A et al. Clinical evaluation of Teronac (mazindol) in the treatment of obesity in children. Part II. Anorectic properties and side effects (author's transl). Przegl Lek 1981; 38: 355–358. | PubMed |
  46. Golebiowska M, Chlebna-Sokol D, Mastalska A, Zwaigzne-Raczynska J. The clinical evaluation of teronac (Mazindol) in the treatment of children with obesity. Part I. Effect of the drug on somatic patterns and exercise capacity (author's transl). Przegl Lek 1981; 38: 311–314. | PubMed |
  47. Komorowski JM, Zwaigzne-Raczynska J, Owczarczyk I, Golebiowska M, Zarzycki J. Effect of mazindol (teronac) on various hormonal indicators in children with simple obesity. Pediatr Pol 1982; 57: 241–246. | PubMed |
  48. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001; 39: 32–41. | Article | PubMed | ISI | CAS |
  49. Kaplan LM. Pharmacologic therapies for obesity. Gastroenterol Clin North Am 2010; 39: 69–79. | Article | PubMed | ISI |
  50. Rothman RB, Ayestas MA, Dersch CM, Baumann MH. Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Circulation 1999; 100: 869–875. | Article | PubMed | ISI | CAS |
  51. Drug Enforcement Administration, Office of Diversion Control. List of scheduling actions controlled substances regulated chemicals, U.S. Department of Justice. Accessed: 1 February 2012.
  52. Altschuler S, Conte A, Sebok M, Marlin RL, Winick C. Three controlled trials of weight loss with phenylpropanolamine. Int J Obes 1982; 6: 549–556. | PubMed |
  53. Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343: 1826–1832. | Article | PubMed | ISI | CAS |
  54. Isojarvi JI, Turkka J, Pakarinen AJ, Kotila M, Rattya J, Myllyla VV. Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 2001; 42: 930–934. | Article | PubMed |
  55. Haas JT, Miao J, Chanda D, Wang Y, Zhao E, Haas ME et al. Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression. Cell Metab 2012; 15: 873–884. | Article | PubMed |
  56. Lorber J. Obesity in childhood. A controlled trial of anorectic drugs. Arch Dis Child 1966; 41: 309–312. | Article | PubMed | ISI |
  57. Stewart DA, Bailey JD, Patell H. Tenuate dospan as an appetitie suppressant in the treatment of obese children. Appl Ther 1970; 12: 34–36. | PubMed |
  58. Malecka-Tendera E, Koehler B, Muchacka M, Wazowski R, Trzciakowska A. Efficacy and safety of dexfenfluramine treatment in obese adolescents. Pediatr Pol 1996; 71: 431–436. | PubMed |
  59. Bacon GE, Lowrey GH. A clinical trial of fenfluramine in obese children. Curr Ther Res Clin Exp 1967; 9: 626–630. | PubMed |
  60. Goldstein DJ, Rampey AH, Enas GG, Potvin JH, Fludzinski LA, Levine LR. Fluoxetine: a randomized clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994; 18: 129–135. | PubMed | CAS |
  61. Pedrinola F, Cavaliere H, Lima N, Medeiros-Neto G. Is DL-fenfluramine a potentially helpful drug therapy in overweight adolescent subjects? Obes Res 1994; 2: 1–4. | PubMed |
  62. Pedrinola F, Sztejnsznajd C, Lima N, Halpern A, Medeiros-Neto G. The addition of dexfenfluramine to fluoxetine in the treatment of obesity: a randomized clinical trial. Obes Res 1996; 4: 549–554. | PubMed |
  63. Rauh JL, Lipp R. Chlorphentermine as an anorexigenic agent in adolescent obesity. Report of its efficacy in a double-blind study of 30 teen-agers. Clin Pediatr (Phila) 1968; 7: 138–140. | Article | PubMed |
  64. Anon. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb Mortal Wkly Rep 1997; 46: 1061–1066.
  65. Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 581–588. | Article | PubMed | ISI | CAS |
  66. Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med 1996; 335: 609–616. | Article | PubMed | ISI | CAS |
  67. Weintraub M, Hasday JD, Mushlin AI, Lockwood DH. A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination. Arch Intern Med 1984; 144: 1143–1148. | Article | PubMed | ISI | CAS |
  68. Mason PW, Krawiecki N, Meacham LR. The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch Pediatr Adolesc Med 2002; 156: 887–892. | PubMed | ISI |
  69. Davis C, Fattore L, Kaplan AS, Carter JC, Levitan RD, Kennedy JL. The suppression of appetite and food consumption by methylphenidate: the moderating effects of gender and weight status in healthy adults. Int J Neuropsychopharmacol 2011; 1–7. | Article | PubMed |
  70. Greenhill LL, Findling RL, Swanson JM. A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 2002; 109: E39. | Article | PubMed |
  71. Wigal T, Greenhill L, Chuang S, McGough J, Vitiello B, Skrobala A et al. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry 2006; 45: 1294–1303. | Article | PubMed |
  72. Klein-Schwartz W. Abuse and toxicity of methylphenidate. Curr Opin Pediatr 2002; 14: 219–223. | Article | PubMed |
  73. Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for obesity: past, current, and future therapies. J Obes 20112011; 179674. | PubMed |
  74. Wald AB, Uli NK. Pharmacotherapy in pediatric obesity: current agents and future directions. Rev Endocr Metab Disord 2009; 10: 205–214. | Article | PubMed | ISI | CAS |
  75. Dunican KC, Desilets AR, Montalbano JK. Pharmacotherapeutic options for overweight adolescents. Ann Pharmacother 2007; 41: 1445–1455. | Article | PubMed |
  76. Godoy-Matos A, Carraro L, Vieira A, Oliveira J, Guedes EP, Mattos L et al. Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study. J Clin Endocrinol Metab 2005; 90: 1460–1465. | Article | PubMed | ISI | CAS |
  77. Violante-Ortiz R, Del-Rio-Navarro BE, Lara-Esqueda A, Perez P, Fanghanel G, Madero A et al. Use of sibutramine in obese Hispanic adolescents. Adv Ther 2005; 22: 642–649. | Article | PubMed |
  78. Berkowitz RI, Fujioka K, Daniels SR, Hoppin AG, Owen S, Perry AC et al. Effects of sibutramine treatment in obese adolescents: a randomized trial. Ann Intern Med 2006; 145: 81–90. | PubMed | ISI | CAS |
  79. Garcia-Morales LM, Berber A, Macias-Lara CC, Lucio-Ortiz C, Del-Rio-Navarro BE, Dorantes-Alvarez LM. Use of sibutramine in obese mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther 2006; 28: 770–782. | Article | PubMed | CAS |
  80. Reisler G, Tauber T, Afriat R, Bortnik O, Goldman M. Sibutramine as an adjuvant therapy in adolescents suffering from morbid obesity. Isr Med Assoc J 2006; 8: 30–32. | PubMed |
  81. Budd GM, Hayman LL, Crump E, Pollydore C, Hawley KD, Cronquist JL et al. Weight loss in obese African American and Caucasian adolescents: secondary analysis of a randomized clinical trial of behavioral therapy plus sibutramine. J Cardiovasc Nurs 2007; 22: 288–296. | PubMed | ISI |
  82. Daniels SR, Long B, Crow S, Styne D, Sothern M, Vargas-Rodriguez I et al. Cardiovascular effects of sibutramine in the treatment of obese adolescents: results of a randomized, double-blind, placebo-controlled study. Pediatrics 2007; 120: e147–e157. | Article | PubMed |
  83. Danielsson P, Janson A, Norgren S, Marcus C. Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes. J Clin Endocrinol Metab 2007; 92: 4101–4106. | Article | PubMed |
  84. Van Mil EG, Westerterp KR, Kester AD, Delemarre-van de Waal HA, Gerver WJ, Saris WH. The effect of sibutramine on energy expenditure and body composition in obese adolescents. J Clin Endocrinol Metab 2007; 92: 1409–1414. | Article | PubMed | CAS |
  85. Yanovski JA. Behavior therapy and sibutramine for the treatment of adolescent obesity. J Pediatr 2003; 143: 686. | Article | PubMed |
  86. Pischon T, Sharma AM. Recent developments in the treatment of obesity-related hypertension. Curr Opin Nephrol Hypertens 2002; 11: 497–502. | Article | PubMed |
  87. Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A et al. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial. Eur Heart J 2007; 28: 2915–2923. | Article | PubMed | ISI |
  88. James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363: 905–917. | Article | PubMed | ISI | CAS |
  89. US Food and Drug Administration. Meridia (sibutramine): Market Withdrawal Due to Risk of SeriousCardiovascular Events. Accessed: 20 October 2010.
  90. Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002; 346: 591–602. | Article | PubMed | ISI | CAS |
  91. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432. | Article | PubMed | ISI | CAS |
  92. Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13: 51–59. | Article | PubMed | ISI | CAS |
  93. Havel PJ, Townsend R, Chaump L, Teff K. High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 1999; 48: 334–341. | Article | PubMed | ISI | CAS |
  94. Weigle DS, Cummings DE, Newby PD, Breen PA, Frayo RS, Matthys CC et al. Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J Clin Endocrinol Metab 2003; 88: 1577–1586. | Article | PubMed | ISI | CAS |
  95. McDuffie JR, Riggs PA, Calis KA, Freedman RJ, Oral EA, DePaoli AM et al. Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency. J Clin Endocrinol Metab 2004; 89: 4258–4263. | Article | PubMed | ISI | CAS |
  96. Schwartz MW. Brain pathways controlling food intake and body weight. Exp Biol Med (Maywood) 2001; 226: 978–981. | PubMed | CAS |
  97. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546. | Article | PubMed | ISI | CAS |
  98. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540–543. | Article | PubMed | ISI | CAS |
  99. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks [see comments]. Science 1995; 269: 546–549. | Article | PubMed | ISI | CAS |
  100. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341: 879–884. | Article | PubMed | ISI | CAS |
  101. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110: 1093–1103. | Article | PubMed | ISI | CAS |
  102. Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab 2004; 89: 4821–4826. | Article | PubMed | ISI | CAS |
  103. Paz-Filho G, Wong ML, Licinio J. Ten years of leptin replacement therapy. Obes Rev 2011; 12: e315–e323. | Article | PubMed | ISI | CAS |
  104. Chong AY, Lupsa BC, Cochran EK, Gorden P. Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia 2010; 53: 27–35. | Article | PubMed | ISI | CAS |
  105. Chou SH, Chamberland JP, Liu X, Matarese G, Gao C, Stefanakis R et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci USA 2011; 108: 6585–6590. | Article | PubMed |
  106. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 1568–1575. | Article | PubMed | ISI | CAS |
  107. Moon HS, Matarese G, Brennan AM, Chamberland JP, Liu X, Fiorenza CG et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 2011; 60: 1647–1656. | Article | PubMed | CAS |
  108. Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002; 87: 2391–2394. | Article | PubMed | ISI | CAS |
  109. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115: 3579–3586. | Article | PubMed | ISI | CAS |
  110. Rosenbaum M, Sy M, Pavlovich K, Leibel RL, Hirsch J. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J Clin Invest 2008; 118: 2583–2591. | PubMed | ISI | CAS |
  111. Goldsmith R, Joanisse DR, Gallagher D, Pavlovich K, Shamoon E, Leibel RL et al. Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. Am J Physiol Regul Integr Comp Physiol 2010; 298: R79–R88. | Article | PubMed | ISI |
  112. Baldwin KM, Joanisse DR, Haddad F, Goldsmith RL, Gallagher D, Pavlovich KH et al. Effects of Weight Loss and Leptin on Skeletal Muscle in Human Subjects. Am J Physiol Regul Integr Comp Physiol 2011; 301: R1259–R1266. | Article | PubMed |
  113. Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O'Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Obes Res 2002; 10: 633–641. | Article | PubMed | ISI | CAS |
  114. Billes SK, Cowley MA. Inhibition of dopamine and norepinephrine reuptake produces additive effects on energy balance in lean and obese mice. Neuropsychopharmacology 2007; 32: 822–834. | Article | PubMed | ISI | CAS |
  115. Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532–546. | PubMed | ISI | CAS |
  116. Jain AK, Kaplan RA, Gadde KM, Wadden TA, Allison DB, Brewer ER et al. Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Obes Res 2002; 10: 1049–1056. | Article | PubMed | ISI | CAS |
  117. Glod CA, Lynch A, Flynn E, Berkowitz C, Baldessarini RJ. Open trial of bupropion SR in adolescent major depression. J Child Adolesc Psychiatr Nurs 2003; 16: 123–130. | Article | PubMed |
  118. Becker EA, Shafer A, Anderson R. Weight changes in teens on psychotropic medication combinations at Austin State Hospital. Tex Med 2005; 101: 62–70. | PubMed |
  119. Martin CK, Redman LM, Zhang J, Sanchez M, Anderson CM, Smith SR et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab 2011; 96: 837–845. | Article | PubMed |
  120. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245–256. | Article | PubMed | ISI | CAS |
  121. Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011; 96: 3067–3077. | Article | PubMed | ISI | CAS |
  122. O'Neil PM, Smith SR, Weissman NJ, Fidler MC, Sanchez M, Zhang J et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 2012; 20: 1426–1436. | Article | PubMed |
  123. Jaslow R FDA approves obesity pill Belviq for obese, overweight people with weight-related health problems. Accessed: 1 July 2012.
  124. FDA. approves Belviq to treat some overweight or obese adults. Accessed: 1 July 2012.
  125. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1906–1913. | Article | PubMed | ISI | CAS |
  126. Gilbert JA, Gasteyger C, Raben A, Meier DH, Astrup A, Sjodin A. The effect of tesofensine on appetite sensations. Obesity 2012; 20: 553–561. | Article | PubMed |
  127. Sjodin A, Gasteyger C, Nielsen AL, Raben A, Mikkelsen JD, Jensen JK et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond) 2010; 34: 1634–1643. | Article | PubMed |
  128. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 2007; 370: 1706–1713. | Article | PubMed | ISI | CAS |
  129. Van Gaal L, Pi-Sunyer X, Despres JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care 2008; 31 (Suppl 2): S229–S240. | Article | PubMed | ISI | CAS |
  130. US Food and Drug Administration. Endocrine and Metabolic Drugs Advisory Committee Meeting. Sanofi Aventis: Zimulti (Rimonabant) Briefing Document - NDA 21-888. May 20, 2007. Accessed: 30 March 2012.
  131. Wathion N European Medicines Agency Public Statement on Acomplia (rimonabant) - Withdrawal of the Marketing Authorisation in European Union, Report Number: EMEA/39457/2009. Accessed: 30 March 2012.
  132. Heal DJ, Gosden J, Smith SL. Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders. Br J Clin Pharmacol 2009; 68: 861–874. | Article | PubMed | CAS |
  133. Koch L. Obesity: Taranabant no longer developed as an antiobesity agent. Nat Rev Endocrinol 2010; 6: 300. | Article | PubMed |
  134. Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J, Jeong WI et al. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 2008; 118: 3160–3169. | Article | PubMed | ISI | CAS |
  135. Nogueiras R, Veyrat-Durebex C, Suchanek PM, Klein M, Tschop J, Caldwell C et al. Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes 2008; 57: 2977–2991. | Article | PubMed | ISI | CAS |
  136. Nakata M, Yada T. Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet beta-cells via CB1 receptors. Regul Pept 2008; 145: 49–53. | Article | PubMed | CAS |
  137. Ruby MA, Nomura DK, Hudak CS, Mangravite LM, Chiu S, Casida JE et al. Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins. Proc Natl Acad Sci USA 2008; 105: 14561–14566. | Article | PubMed |
  138. Kramer CK, Leitao CB, Pinto LC, Canani LH, Azevedo MJ, Gross JL. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev 2011; 12: e338–e347. | Article | PubMed |
  139. Narula PK, Rehan HS, Unni KE, Gupta N. Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: a double-blind, placebo-controlled trial. Schizophr Res 2010; 118: 218–223. | Article | PubMed |
  140. Glauser TA, Dlugos DJ, Dodson WE, Grinspan A, Wang S, Wu SC. Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents. J Child Neurol 2007; 22: 693–699. | Article | PubMed |
  141. Ferraro D, Di Trapani G. Topiramate in the prevention of pediatric migraine: literature review. J Headache Pain 2008; 9: 147–150. | Article | PubMed |
  142. Lessig MC, Shapira NA, Murphy TK. Topiramate for reversing atypical antipsychotic weight gain. J Am Acad Child Adolesc Psychiatry 2001; 40: 1364. | Article | PubMed | CAS |
  143. Pavuluri MN, Janicak PG, Carbray J. Topiramate plus risperidone for controlling weight gain and symptoms in preschool mania. J Child Adolesc Psychopharmacol 2002; 12: 271–273. | Article | PubMed |
  144. Canitano R. Clinical experience with Topiramate to counteract neuroleptic induced weight gain in 10 individuals with autistic spectrum disorders. Brain Dev 2005; 27: 228–232. | Article | PubMed |
  145. Carter GT, Yudkowsky MP, Han JJ, McCrory MA. Topiramate for weight reduction in Duchenne muscular dystrophy. Muscle Nerve 2005; 31: 788–789. | Article | PubMed |
  146. Nathan PJ, O'Neill BV, Napolitano A, Bullmore ET. Neuropsychiatric adverse effects of centrally acting antiobesity drugs. CNS Neurosci Ther 2011; 17: 490–505. | Article | PubMed |
  147. Fountain NB. A pregnant pause to consider teratogenicity of topiramate. Epilepsy Curr 2009; 9: 36–38. | Article | PubMed |
  148. Roberts MD US Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee Clinical Briefing Document February 22, 2012. VIVUS, Inc. New Drug Application 22580: VI-0521 QNEXA (phentermine/topiramate). Aaccessed: 30 March 2012.
  149. Potes CS, Lutz TA. Brainstem mechanisms of amylin-induced anorexia. Physiol Behav 2010; 100: 511–518. | Article | PubMed |
  150. Hay DL, Christopoulos G, Christopoulos A, Sexton PM. Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans 2004; 32 (Partt 5): 865–867. | Article | PubMed | ISI | CAS |
  151. Singh-Franco D, Perez A, Harrington C. The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2011; 13: 169–180. | Article | PubMed |
  152. Maggs D, Shen L, Strobel S, Brown D, Kolterman O, Weyer C. Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis. Metabolism 2003; 52: 1638–1642. | Article | PubMed |
  153. Aronne L, Fujioka K, Aroda V, Chen K, Halseth A, Kesty NC et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007; 92: 2977–2983. | Article | PubMed | ISI | CAS |
  154. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008; 31: 1816–1823. | Article | PubMed | ISI |
  155. Chase HP, Lutz K, Pencek R, Zhang B, Porter L. Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study. J Pediatr 2009; 155: 369–373. | Article | PubMed | ISI | CAS |
  156. Kishiyama CM, Burdick PL, Cobry EC, Gage VL, Messer LH, McFann K et al. A pilot trial of pramlintide home usage in adolescents with type 1 diabetes. Pediatrics 2009; 124: 1344–1347. | Article | PubMed |
  157. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992. | Article | PubMed | ISI | CAS |
  158. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002; 8: 643–644. | Article | PubMed | ISI | CAS |
  159. De Waele K, Ishkanian SL, Bogarin R, Miranda CA, Ghatei MA, Bloom SR et al. Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome. Eur J Endocrinol 2008; 159: 381–388. | Article | PubMed | ISI | CAS |
  160. Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374: 1606–1616. | Article | PubMed | ISI | CAS |
  161. Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care 2009; 32: 1224–1230. | Article | PubMed | ISI | CAS |
  162. Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia 2009; 52: 2046–2055. | Article | PubMed | ISI | CAS |
  163. Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R. Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care 2009; 32: 1237–1243. | Article | PubMed | CAS |
  164. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009; 32: 84–90. | Article | PubMed | ISI | CAS |
  165. Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009; 373: 473–481. | Article | PubMed | ISI | CAS |
  166. Taylor K, Gurney K, Han J, Pencek R, Walsh B, Trautmann M. Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years. BMC Endocr Disord 2011; 11: 9. | Article | PubMed |
  167. Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K et al. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care 2010; 33: 1173–1175. | Article | PubMed | ISI |
  168. Kelly AS, Metzig AM, Rudser KD, Fitch AK, Fox CK, Nathan BM et al. Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study. Obesity (Silver Spring) 2012; 20: 364–370. | Article | PubMed |
  169. Mathis LL US Food and Drug Administration. Pediatric Advisory Committee Meeting March 22, 2010. Orlistat Update. Accessed: 30 March 2012.
  170. McDuffie JR, Calis KA, Uwaifo GI, Sebring NG, Fallon EM, Hubbard VS et al. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res 2002; 10: 642–650. | Article | PubMed | CAS |
  171. Zhi J, Moore R, Kanitra L. The effect of short-term (21-day) orlistat treatment on the physiologic balance of six selected macrominerals and microminerals in obese adolescents. J Am Coll Nutr 2003; 22: 357–362. | PubMed |
  172. Norgren S, Danielsson P, Jurold R, Lotborn M, Marcus C. Orlistat treatment in obese prepubertal children: a pilot study. Acta Paediatr 2003; 92: 666–670. | Article | PubMed | CAS |
  173. Ozkan B, Bereket A, Turan S, Keskin S. Addition of orlistat to conventional treatment in adolescents with severe obesity. Eur J Pediatr 2004; 163: 738–741. | Article | PubMed | ISI |
  174. McDuffie JR, Calis KA, Uwaifo GI, Sebring NG, Fallon EM, Frazer TE et al. Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions. J Pediatr Endocrinol Metab 2004; 17: 307–319. | Article | PubMed | CAS |
  175. Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. Jama 2005; 293: 2873–2883. | Article | PubMed | ISI | CAS |
  176. Maahs D, de Serna DG, Kolotkin RL, Ralston S, Sandate J, Qualls C et al. Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocr Pract 2006; 12: 18–28. | PubMed |
  177. Chanoine JP, Richard M. Early weight loss and outcome at one year in obese adolescents treated with orlistat or placebo. Int J Pediatr Obes 2011; 6: 95–101. | Article | PubMed |
  178. Yanovski JA, McDuffie JR, Salaita CS, Tanofsky-Kraff M, Sebring NG, Young-Hyman D et al. A randomized, placebo-controlled trial of the effects of orlistat on body weight and body composition in African American and Caucasian adolescents with obesity-related comorbid conditions. Obesity 2008; 16 (Suppl. 1): S63.
  179. Umemura T, Ichijo T, Matsumoto A, Kiyosawa K. Severe hepatic injury caused by orlistat. Am J Med 2006; 119: e7. | Article | PubMed |
  180. Forrester MB. Pattern of orlistat exposures in children aged 5 years or less. J Emerg Med 2009; 37: 396–399. | Article | PubMed |
  181. O'Connor MB. An orlistat ‘overdose’ in a child. Ir J Med Sci 2010; 179: 315. | Article | PubMed |
  182. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27: 155–161. | Article | PubMed | ISI | CAS |
  183. McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy 2002; 22: 814–822. | Article | PubMed |
  184. FDA. Approves Orlistat for Over-the-Counter Use. Accessed: 9 July 2012.
  185. Kopelman P, Bryson A, Hickling R, Rissanen A, Rossner S, Toubro S et al. Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients. Int J Obes (Lond) 2007; 31: 494–499. | Article | PubMed | CAS |
  186. Kopelman P, Groot Gde H, Groot G, Rissanen A, Rossner S, Toubro S et al. Weight loss, HbA 1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (xenical). Obesity 2010; 18: 108–115. | Article | PubMed |
  187. Kopelman P, Groot Gde H, Rissanen A, Rossner S, Toubro S, Palmer R et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring) 2010; 18: 108–115. | Article | PubMed | CAS |
  188. Salvatore T, Giugliano D. Pharmacokinetic-pharmacodynamic relationships of Acarbose. Clin Pharmacokinet 1996; 30: 94–106. | Article | PubMed |
  189. Wang JS, Lin SD, Lee WJ, Su SL, Lee IT, Tu ST et al. Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison. Clin Ther 2011; 33: 1932–1942. | Article | PubMed |
  190. Wolever TM, Chiasson JL, Josse RG, Hunt JA, Palmason C, Rodger NW et al. Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes. Int J Obes Relat Metab Disord 1997; 21: 756–763. | Article | PubMed |
  191. Tugrul S, Kutlu T, Pekin O, Baglam E, Kiyak H, Oral O.. Clinical, endocrine, and metabolic effects of acarbose, a alpha-glucosidase inhibitor, in overweight and nonoverweight patients with polycystic ovarian syndrome. Fertil Steril 2008; 90: 1144–1148. | Article | PubMed |
  192. Hussey EK, Clark RV, Amin DM, Kipnes MS, O'Connor-Semmes RL, O'Driscoll EC et al. Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with type 2 diabetes mellitus. J Clin Pharmacol 2010; 50: 623–635. | Article | PubMed |
  193. Hussey EK, Dobbins RL, Stoltz RR, Stockman NL, O'Connor-Semmes RL, Kapur A et al. Multiple-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy overweight and obese subjects: a randomized double-blind study. J Clin Pharmacol 2010; 50: 636–646. | Article | PubMed | CAS |
  194. Komoroski B, Vachharajani N, Boulton D, Kornhauser D, Geraldes M, Li L et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther 2009; 85: 520–526. | Article | PubMed | ISI | CAS |
  195. Zhang L, Feng Y, List J, Kasichayanula S, Pfister M. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes Metab 2010; 12: 510–516. | Article | PubMed | ISI | CAS |
  196. Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011; 13: 928–938. | Article | PubMed | ISI | CAS |
  197. Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34: 2015–2022. | Article | PubMed | ISI | CAS |
  198. Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012; 97: 1020–1031. | Article | PubMed |
  199. Grogan K FDA panel rejects B-MS/AZ's diabetes drug...but only just. Pharma Times Online. Published on-line 07/20/2011 Accessed: 25 November 2011.
  200. Mehnert H. Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance. Exp Clin Endocrinol Diabetes 2001; 109 (Suppl 2): S259–S264. | Article | PubMed | CAS |
  201. Hundal RS, Inzucchi SE. Metformin: new understandings, new uses. Drugs 2003; 63: 1879–1894. | Article | PubMed | ISI | CAS |
  202. Bestermann W, Houston MC, Basile J, Egan B, Ferrario CM, Lackland D et al. Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome. Am J Med Sci 2005; 329: 292–305. | Article | PubMed |
  203. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403. | Article | PubMed | ISI | CAS |
  204. Rezvanian H, Hashemipour M, Kelishadi R, Tavakoli N, Poursafa P. A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity. World J Pediatr 2010; 6: 317–322. | Article | PubMed |
  205. Freemark M, Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics 2001; 107: E55. | Article | PubMed | CAS |
  206. Wilson DM, Abrams SH, Aye T, Lee PD, Lenders C, Lustig RH et al. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Arch Pediatr Adolesc Med 2010; 164: 116–123. | Article | PubMed | ISI |
  207. Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes 2011; 60: 477–485. | Article | PubMed | ISI | CAS |
  208. Fu JF, Liang L, Zou CC, Hong F, Wang CL, Wang XM et al. Prevalence of the metabolic syndrome in Zhejiang Chinese obese children and adolescents and the effect of metformin combined with lifestyle intervention. Int J Obes (Lond) 2007; 31: 15–22. | Article | PubMed |
  209. Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab 2008; 21: 339–348. | Article | PubMed | ISI | CAS |
  210. Clarson CL, Mahmud FH, Baker JE, Clark HE, McKay WM, Schauteet VD et al. Metformin in combination with structured lifestyle intervention improved body mass index in obese adolescents, but did not improve insulin resistance. Endocrine 2009; 36: 141–146. | Article | PubMed |
  211. Wiegand S, l'Allemand D, Hubel H, Krude H, Burmann M, Martus P et al. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. Eur J Endocrinol 2010; 163: 585–592. | Article | PubMed |
  212. Legro RS. Impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women: do we need a new drug? J Clin Endocrinol Metab 2008; 93: 4218–4220. | Article | PubMed |
  213. Mastorakos G, Koliopoulos C, Deligeoroglou E, Diamanti-Kandarakis E, Creatsas G. Effects of two forms of combined oral contraceptives on carbohydrate metabolism in adolescents with polycystic ovary syndrome. Fertil Steril 2006; 85: 420–427. | Article | PubMed |
  214. Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008; 93: 4299–4306. | Article | PubMed |
  215. Ibanez L, de Zegher F. Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 2004; 89: 1592–1597. | Article | PubMed | CAS |
  216. Bridger T, MacDonald S, Baltzer F, Rodd C. Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. Arch Pediatr Adolesc Med 2006; 160: 241–246. | Article | PubMed |
  217. Allen HF, Mazzoni C, Heptulla RA, Murray MA, Miller N, Koenigs L et al. Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab 2005; 18: 761–768. | Article | PubMed | CAS |
  218. Arslanian SA, Lewy V, Danadian K, Saad R. Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 2002; 87: 1555–1559. | Article | PubMed | CAS |
  219. Klein DJ, Cottingham EM, Sorter M, Barton BA, Morrison JA. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry 2006; 163: 2072–2079. | Article | PubMed |
  220. Bjorkhem-Bergman L, Asplund AB, Lindh JD. Metformin for weight reduction in non-diabetic patients on antipsychotic drugs: a systematic review and meta-analysis. J Psychopharmacol 2011; 25: 299–305. | Article | PubMed |
  221. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: the national health and nutrition examination survey, 1999–2006. Diabetes Care 2012; 35: 327–333. | Article | PubMed |
  222. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010; 4, CD002967.
  223. Gambineri A, Patton L, De Iasio R, Cantelli B, Cognini GE, Filicori M et al. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 3854–3862. | Article | PubMed |
  224. Haqq AM, Stadler DD, Rosenfeld RG, Pratt KL, Weigle DS, Frayo RS et al. Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab 2003; 88: 3573–3576. | Article | PubMed | ISI | CAS |
  225. Dietz J, Schwartz J. Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes. Metabolism 1991; 40: 800–806. | Article | PubMed | CAS |
  226. Snel YE, Doerga ME, Brummer RJ, Zelissen PM, Zonderland ML, Koppeschaar HP. Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy. Eur J Endocrinol 1995; 133: 445–450. | Article | PubMed |
  227. Gregory JW, Greene SA, Jung RT, Scrimgeour CM, Rennie MJ. Changes in body composition and energy expenditure after six weeks' growth hormone treatment. Arch Dis Child 1991; 66: 598–602. | Article | PubMed |
  228. Hoos MB, Westerterp KR, Gerver WJ. Short-term effects of growth hormone on body composition as a predictor of growth. J Clin Endocrinol Metab 2003; 88: 2569–2572. | Article | PubMed |
  229. Eden Engstrom B, Burman P, Holdstock C, Karlsson FA. Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients. J Clin Endocrinol Metab 2003; 88: 5193–5198. | Article | PubMed |
  230. Hoybye C, Hilding A, Jacobsson H, Thoren M. Growth hormone treatment improves body composition in adults with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2003; 58: 653–661. | Article | PubMed |
  231. Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab 2002; 87: 1581–1585. | Article | PubMed | CAS |
  232. Myers SE, Davis A, Whitman BY, Santiago JV, Landt M. Leptin concentrations in Prader-Willi syndrome before and after growth hormone replacement. Clin Endocrinol (Oxf) 2000; 52: 101–105. | Article | PubMed |
  233. Shadid S, Jensen MD. Effects of growth hormone administration in human obesity. Obes Res 2003; 11: 170–175. | Article | PubMed | CAS |
  234. Bell J, Parker KL, Swinford RD, Hoffman AR, Maneatis T, Lippe B. Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab 2010; 95: 167–177. | Article | PubMed | ISI | CAS |
  235. Lammer C, Weimann E. [Changes in carbohydrate metabolism and insulin resistance in patients with Prader-Willi Syndrome (PWS) under growth hormone therapy]. Wien Med Wochenschr 2007; 157: 82–88. | Article | PubMed |
  236. Hauffa BP, Knaup K, Lehmann N, Neudorf U, Nagel B. Effects of growth hormone therapy on cardiac dimensions in children and adolescents with Prader-Willi syndrome. Horm Res Paediatr 2011; 75: 56–62. | Article | PubMed |
  237. Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab 2006; 91: 413–417. | Article | PubMed | CAS |
  238. Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken-Koelega AC. Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab 2006; 91: 4911–4915. | Article | PubMed | ISI |
  239. Genotropin (somatropin [rDNA origin] for injection). Accessed: 10 Jyly 2012.
  240. US Food and Drug Administration.. MedWatch The FDA Safety Information and Adverse Event Reporting Program. Recombinant Human Growth Hormone (somatropin): Ongoing Safety Review - Possible Increased Risk of Death. Posted 12/22/2010. Accessed: 30 March 2012.
  241. Bray GA, Greenway FL. Current and potential drugs for treatment of obesity. Endocr Rev 1999; 20: 805–875. | Article | PubMed | ISI | CAS |
  242. Krotkiewski M. Thyroid hormones and treatment of obesity. Int J Obes Relat Metab Disord 2000; 24 (Suppl 2): S116–S119. | Article | PubMed |
  243. Bhasin S, Wallace W, Lawrence JB, Lesch M. Sudden death associated with thyroid hormone abuse. Am J Med 1981; 71: 887–890. | Article | PubMed | CAS |
  244. Baxter JD, Webb P, Grover G, Scanlan TS. Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. Trends Endocrinol Metab 2004; 15: 154–157. | Article | PubMed | ISI | CAS |
  245. Berkenstam A, Kristensen J, Mellstrom K, Carlsson B, Malm J, Rehnmark S et al. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc Natl Acad Sci USA 2008; 105: 663–667. | Article | PubMed |
  246. Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH et al. Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr 2002; 76: 780–788. | PubMed | ISI | CAS |
  247. Redman LM, de Jonge L, Fang X, Gamlin B, Recker D, Greenway FL et al. Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J Clin Endocrinol Metab 2007; 92: 527–531. | Article | PubMed |
  248. Buemann B, Toubro S, Astrup A. Effects of the two beta3-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects. Int J Obes Relat Metab Disord 2000; 24: 1553–1560. | Article | PubMed |
  249. Astrup A. Thermogenic drugs as a strategy for treatment of obesity. Endocrine 2000; 13: 207–212. | Article | PubMed | ISI | CAS |
  250. Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002; 26: 593–604. | Article | PubMed | CAS |
  251. Greenway FL, Bray GA. Treatment of hypothalamic obesity with caffeine and ephedrine. Endocr Pract 2008; 14: 697–703. | PubMed |
  252. Molnar D, Torok K, Erhardt E, Jeges S. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord 2000; 24: 1573–1578. | Article | PubMed |
  253. McBride BF, Karapanos AK, Krudysz A, Kluger J, Coleman CI, White CM. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004; 291: 216–221. | Article | PubMed | ISI | CAS |
  254. Pasman WJ, Westerterp-Plantenga MS, Saris WH. The effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenance. Int J Obes Relat Metab Disord 1997; 21: 1143–1151. | Article | PubMed | CAS |
  255. Daly PA, Krieger DR, Dulloo AG, Young JB, Landsberg L. Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord 1993; 17 (Suppl 1): S73–S78. | PubMed |
  256. Hackman RM, Havel PJ, Schwartz HJ, Rutledge JC, Watnik MR, Noceti EM et al. Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial. Int J Obes (Lond) 2006; 30: 1545–1556. | Article | PubMed |
  257. Toubro S, Astrup AV, Breum L, Quaade F. Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture. Int J Obes Relat Metab Disord 1993; 17 (Suppl 1): S69–S72. | PubMed |
  258. Norregaard J, Jorgensen S, Mikkelsen KL, Tonnesen P, Iversen E, Sorensen T et al. The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain. Clin Pharmacol Ther 1996; 60: 679–686. | Article | PubMed |
  259. Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond) 2007; 31: 121–130. | Article | PubMed |
  260. Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev 2001; 2: 199–211. | Article | PubMed | CAS |
  261. Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clin Pharmacol Ther 1992; 51: 581–585. | Article | PubMed | ISI | CAS |
  262. Weintraub M, Sundaresan PR, Schuster B, Averbuch M, Stein EC, Cox C et al. Long-term weight control study. IV (weeks 156 to 190). The second double-blind phase. Clin Pharmacol Ther 1992; 51: 608–614. | Article | PubMed | CAS |
  263. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 1341–1352. | Article | PubMed | ISI | CAS |
  264. Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012; 95: 297–308. | Article | PubMed | CAS |
  265. Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2011; 2: 330–342.
  266. Lazarus R, Baur L, Webb K, Blyth F. Adiposity and body mass indices in children: Benn's index and other weight for height indices as measures of relative adiposity. Int J Obes Relat Metab Disord 1996; 20: 406–412. | PubMed | CAS |
  267. FDA. approves weight-management drug Qsymia. Accessed: 18 July 2012.
  268. Gadde KM, Yonish GM, Foust MS, Wagner HR. Combination therapy of zonisamide and bupropion for weight reduction in obese women: a preliminary, randomized, open-label study. J Clin Psychiatry 2007; 68: 1226–1229. | Article | PubMed | ISI |
  269. Greenway FL, Whitehouse MJ, Guttadauria M, Anderson JW, Atkinson RL, Fujioka K et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring) 2009; 17: 30–39. | Article | PubMed | CAS |
  270. Hjalmarsen A, Aasebo U, Birkeland K, Sager G, Jorde R. Impaired glucose tolerance in patients with chronic hypoxic pulmonary disease. Diabetes Metab 1996; 22: 37–42. | PubMed |
  271. Orexigen Therapeutics Inc. CONTRAVE (Naltrexone SR/Bupropion SR combination). Endocrinologic and Metabolic Drugs Advisory Committee briefing document. NDA 200063 Accessed: 1 February 2012.
  272. Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM et al. Weight loss with naltrexone SR/Bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011; 19: 110–120. | Article | PubMed |
  273. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376: 595–605. | Article | PubMed | ISI | CAS |
  274. Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011; 19: 110–120. | Article | PubMed |
  275. Padwal R. Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. Curr Opin Investig Drugs 2009; 10: 1117–1125. | PubMed |
  276. Tran PT, Thomas A. Summary Minutes of the Endocrinologic and Metabolic Drugs Advisory Committee. U.S. Food and Drug Administration Center for Drug Evaluation and Research. U.S. Food and Drug AdministrationSilver Spring, Maryland, 2010. pp 1–8, Accessed: 5 November 2011.
  277. Ware C. FDA Won't Approve Weight Loss Drug Contrave-Agency Asks for More Studies to Check for Heart Attack Risk. WebMD Accessed: 1 February 2012.
  278. Orexigen Therapeutics, Inc. Orexigen Announces Agreement From the FDA on a Special Protocol Assessment for the Contrave Outcomes Trial. Accessed: 6 February 2012.
  279. Ravussin E, Smith SR, Mitchell JA, Shringarpure R, Shan K, Maier H et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 2009; 17: 1736–1743. | Article | PubMed |
  280. Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 2008; 105: 7257–7262. | Article | PubMed |
  281. Roth JD, Trevaskis JL, Wilson J, Lei C, Athanacio J, Mack C et al. Antiobesity effects of the beta-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats. Int J Obes (Lond) 2008; 32: 1201–1210. | Article | PubMed | CAS |
  282. Aronne LJ, Halseth AE, Burns CM, Miller S, Shen LZ. Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial. Obesity (Silver Spring) 2010; 18: 1739–1746. | Article | PubMed |
  283. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937–948. | Article | PubMed | ISI | CAS |
  284. den Hoed M, Ekelund U, Brage S, Grontved A, Zhao JH, Sharp SJ et al. Genetic susceptibility to obesity and related traits in childhood and adolescence: influence of loci identified by genome-wide association studies. Diabetes 2010; 59: 2980–2988. | Article | PubMed | ISI | CAS |
  285. Zhao J, Bradfield JP, Zhang H, Sleiman PM, Kim CE, Glessner JT et al. Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity (Silver Spring) 2011; 19: 2436–2439. | Article | PubMed |
  286. Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27: 2121–2158. | Article | PubMed | ISI | CAS |
  287. Skelton JA, Beech BM. Attrition in paediatric weight management: a review of the literature and new directions. Obes Rev 2011; 12: e273–e281. | Article | PubMed |
  288. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Bmj 2010; 340: c332. | Article | PubMed |
  289. Cole TJ, Faith MS, Pietrobelli A, Heo M. What is the best measure of adiposity change in growing children: BMI, BMI %, BMI z-score or BMI centile? Eur J Clin Nutr 2005; 59: 419–425. | Article | PubMed | ISI | CAS |
  290. Berkey CS, Colditz GA. Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies. Ann Epidemiol 2007; 17: 44–50. | Article | PubMed | ISI |
  291. Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord 2002; 26: 262–273. | Article | PubMed | CAS |
  292. Franz MJ, VanWormer JJ, Crain AL, Boucher JL, Histon T, Caplan W et al. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc 2007; 107: 1755–1767. | Article | PubMed | ISI |
  293. Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med 2009; 26: 268–278. | Article | PubMed | ISI | CAS |
  294. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374: 39–47. | Article | PubMed | ISI | CAS |
  295. Choy M, Lam S. Sitagliptin: a novel drug for the treatment of type 2 diabetes. Cardiol Rev 2007; 15: 264–271. | Article | PubMed |
  296. Perez-Monteverde A, Seck T, Xu L, Lee MA, Sisk CM, Williams-Herman DE et al. Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naive patients with type 2 diabetes. Int J Clin Pract 2011; 65: 930–938. | Article | PubMed |
  297. Sloth B, Davidsen L, Holst JJ, Flint A, Astrup A. Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males. Am J Physiol Endocrinol Metab 2007; 293: E604–E609. | Article | PubMed | ISI | CAS |
  298. Gantz I, Erondu N, Mallick M, Musser B, Krishna R, Tanaka WK et al. Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. J Clin Endocrinol Metab 2007; 92: 1754–1757. | Article | PubMed | CAS |
  299. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010; 375: 2223–2233. | Article | PubMed | ISI | CAS |


The conduct of this research was supported by Intramural Research Program Grant 1ZIAHD000641 from the NICHD (to JA Yanovski).

Supplementary Information accompanies the paper on International Journal of Obesity website

Extra navigation