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Long-term maintenance of weight loss with sibutramine in a GP setting following a specialist guided very-low-calorie diet: a double-blind, placebo-controlled, parallel group study

European Journal of Clinical Nutrition volume 59, pages S31–S39 (2005)Cite this article

Abstract

Objective:

Very-low-calorie diets (VLCDs) are used to promote short-term weight loss in obese patients. However, long-term maintenance of weight loss is generally poor. We assessed the efficacy and safety of sibutramine in maintaining weight loss achieved in obese patients by means of a 3-month VLCD.

Design:

A multicenter double-blind, parallel-group trial conducted over 18 months, following a 3-month open label VLCD run-in.

Setting:

Eight hospital centers in The Netherlands, with subsequent follow-up in general practice.

Subjects:

A total of 221 obese subjects, of whom 189 were randomized (mean screening BMI 36.6 kg/m2; mean age 42.6 y).

Measurements:

Patients were given a 3-month VLCD and were required to lose 10% or more of their initial weight. A total of 189 patients completed this phase (mean percentage weight loss 14.5±3.2%) and were randomized to sibutramine 10 mg/day (n=94) or matching placebo (n=95). All patients received a recommended diet and exercise program. The primary analysis was outcome in terms of achieving 80% weight maintenance of the VLCD period at month 18. Secondary analysis was percentage of initial weight loss maintained at months 6, 12, 18 and end point.

Results:

At month 18, the odds ratio for achieving successful weight maintenance was 1.76 (95% CI 1.06, 2.93) in favor of sibutramine (P=0.03). In intention-to-treat analysis, more than 80% of the weight loss achieved during the VLCD phase was maintained by 70, 51 and 30% of sibutramine-treated patients at months 6, 12 and 18, respectively, compared to 48, 31 and 20% of placebo-treated patients. The differences between the treatment groups were significant (P≤0.03) at all time points.

Conclusion:

Weight loss achieved with a VLCD is more effectively maintained with sibutramine in combination with a recommended diet and exercise program than with placebo over a follow-up period of 18 months. Sibutramine is well tolerated, with a safety profile consistent with that seen in other previous trials.

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Acknowledgements

The investigators would like to thank all the patients for their participation in this study. This study was funded by Knoll BV (now Abbott BV), the manufacturer of sibutramine. The VLCD used in the study (Modifast) was supplied by Novartis Medical Nutrition.

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Authors and Affiliations

  1. Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    E M H Mathus-Vliegen

Authors
  1. E M H Mathus-Vliegen
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for the Balance Study Group

Corresponding author

Correspondence to E M H Mathus-Vliegen.

Additional information

Contributors: Professor Dr *EMHM-V (Academic Medical Center) was the principal investigator and led the overall implementation of the trial. Co-principal investigators in hospital centres throughout the Netherlands were Dr GH de Groot, Beverwijk; Dr RPLM Hoogma, Gouda; Dr PFMJ Spooren, Tilburg; Dr PMJ Zelissen, Utrecht; Dr J Wolthuis and Dr AJJ Woittiez, Almelo; Dr W Venekamp, Brunssum; Dr PWE Haeck, Stadskanaal. Follow-up was conducted in primary care by general practitioners and dietitians. Amsterdam: Mr FCJ Sluyter, Amsterdam; Mrs B Dekker, Badhoevedorp; Mr NO Baden, Abcoude; Mrs HGA Jochemsen-van der Leeuw, Weesp; Mrs A Bruce, Amsterdam; Mr DA van der Kwaak, Almere; Mrs YEV van Hazel, Amsterdam; Mrs CW Nijkerk, Amsterdam; Mrs L Podzimek, Ouderkerk a/d Amstel; Mr T de Gee, Amstelveen; Mr P van der Veen, Amsterdam; Mrs C Belmer, Slotermeer; Mr W Venneman, Amsterdam; Mrs P vd Burg, Amsterdam. Beverwijk: Mr CY Schutte, Heemskerk; Mrs J Kuiper-Mes, Assendelft; Mr P Buitenhuis, Castricum; Mr WM Steenhuisen, Heemskerk; Mr DHR Doeksen, Castricum; Mr FM van Velzen, Beverwijk; Mr HW van Faassen, Velserbroek; Mr GJ Vos, Beverwijk; Mrs ND Martijnse, Krommenie; Mr DJ van Wijk, Uitgeest; Mr FB Naber, Heemskerk; Mrs L Sprengers, Heemskerk; Mr AB van Oudvorst, Wijk aan Zee; Mrs L Smit, Velserbroek. Gouda: Mr D Jongekrijg, Nieuwerkerk a/d IJssel; Mrs E Fiolet-van Wingerden, Linschoten; Mr GJP Bloemen, Gouda; Mrs D van Puijenbroek, Zoetermeer; Mr WA van Heel, Waddinxveen; Mrs MM Castricum-Noordam, Nieuwerkerk a/d IJssel; Mr GJ de Jong, Reeuwijk; Mrs K Blauw-Bots/Mrs MM van der Geest-Rensen, Alphen a/d Rijn; Mr RL Warnaar, Bleiswijk. Tilburg: Mrs T van Andel-van Delft, Rosmalen; Mr PAJM Emmers, Den Bosch; Mrs R Heling, Oosterhout; Mr ACPM van Gorp, Tilburg; Mrs Keusters, Gilze; Mr GWLM Verhaak, Tilburg; Mrs G Kobussen-Kuyper, Rosmalen; Mr CJH Broekmeulen, Den Bosch; Mr JB Vossenberg, Breda; Mr HJ van der Krabben, Den Bosch. Utrecht: Mrs RD van den Broek-Hartsuiker, Nieuwegein; Mr KM van den Berg, Utrecht; Mr FJ van den Broek, Nieuwegein; Mrs T Geerets, Tienhoven; Mrs CE Harms, Wijk bij Duurstede; Mr R van Dehn, Hilversum; Mrs L Mooyman-Coren, Hilversum; Mr GPM Ettes, Zeist; Mr JHH Overbeek, Soest. Almelo: Mrs I Verwey, Enschede; Mr AJM Boermans, Losser; Mrs ACM Rijk-Marquering, Nijverdal; Mr V Coopman, Almelo; Mrs Werner-Boelens, Hengelo; Mr PA Schreuder, Rijssen; Mr J Veerman, Nijverdal; Mr HL Jaarsma, Enschede; Mr JLM de Roos, Delden. Brunssum: Mr AJM Vluggen, Kerkrade; Mrs M Lomme, Born; Mr PGJ van Aubel, Heerlen; Mr HWMP Bergmans, Geleen; Mr RAY van Rooij, Maastricht; Mr MMJ Dirckx, Geleen; Mr RJMG Costongs, Voerendaal; Mr TSA Hellemons, Geleen; Mr PHM Passage, Kerkrade; Mr M Op den Kamp, Heerlen; Mrs JHMG Nijskens-Kleinen, Hoensbroek; Mr AGJM Roos, Brunssum; Mrs I Houben, Maastricht. Stadskanaal: J Hilbrands, Emmen; Mr HJAM Fransen, Musselkanaal; Mr P Muilwijk, Emmen; Mr H Prak, Musselkanaal; Mr AH Vlietstra, Nieuwe Pekela; Mr WL Feis, Oude Pekela; Mrs R Trip, Stadskanaal. The study was coordinated by Dr E Geervliet, Scientific Affairs Manager, Abbott BV, 2132 WT Hoofddorp, The Netherlands. Statistical assistance was provided by Ms Sajda Ghani. The principal investigator, Professor Dr EMH Mathus-Vliegen, was responsible for interpretation of the data and preparation of the manuscript.

Discussion after Mathus-Vliegen

Helman: How much support from the GP and the dietitian did each patient receive?

Mathus: In the beginning this was every 2 weeks, and after 5 months it was every month. The GP took 15 min, and for the dietitian it was dependent on how the patient was doing.

Kok: Did you see the patients after the study? And how was their weight then?

Mathus: If you stop treating, of course the weight will go up again. If you stop the insulin in a diabetes patient, the diabetes comes back. Obesity is a noncurable metabolic disease. If you stop the treatment, patients will gain weight. We saw the patients 1 month after the study, and then they had not gained weight yet, but I presume a year after the study they will.

Kok: What I found very impressive is this very-low-calorie diet, with 500 kcal/day for 3 months. You must have used a huge motivational interview technique. How did you manage?

Mathus: The patients did even better than we asked for; we wanted them to lose 10%; they asked us to change that to 15%. We saw the GPs and the dietitians twice in extended evening meetings. The patients were also seen twice in evening meetings. So they were very much aware of the protocol.

Kok: So for the usual practice of a GP, this would be too intensive?

Mathus: I do not agree. If GPs would work together more with dietitians who can much better manage the patients because of less time restrictions, I think this can be done. And it has been done afterwards by GPs who participated in the study and repeated the study. They did not have this enormous success, but still saw their patients were losing weight as they did in the study.

Van Binsbergen: Do you think the practice nurse will have a big role in this matter, between the GP and the dietitian?

Mathus: Absolutely.

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Mathus-Vliegen, E., for the Balance Study Group. Long-term maintenance of weight loss with sibutramine in a GP setting following a specialist guided very-low-calorie diet: a double-blind, placebo-controlled, parallel group study. Eur J Clin Nutr 59 (Suppl 1), S31–S39 (2005). https://doi.org/10.1038/sj.ejcn.1602172

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