Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status

doi:doi:10.1038/sj.ijo.0803498

Abstract

Background:

Obesity treatment with single drugs produces weight losses of about 8–10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen–fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine–fluoxetine (phen–flu) has been proposed as an alternative for phen–fen.

Objective:

To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen–flu vs phen–fen.

Design:

Retrospective chart review of all patients treated for at least 3 months with phen–flu (N=97) to a random sample of patients treated with phen–fen (N=98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen–flu (N=21) to a random sample of patients treated with phen–fen (N=47), and to a group of subjects never treated with obesity drugs (N=26).

Results:

With last observation carried forward analysis (LOCF), at 6 months of treatment the phen–fen patients lost 12.6 plusminus 0.6% of baseline weight and phen–flu patients lost 9.00.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.40.6 vs 13.30.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m² for phen–fen and phen–flu, respectively (P<0.001), and 6.2 plusminus 0.3 vs 5.40.4 kg/m², respectively, for the completers analysis (P – NS). Dropout rate at 6 months was higher in phen–flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen–fen subjects and in none of 15 phen–flu subjects or 25 control subjects who had not been treated with drugs.

Conclusions:

The combination of phentermine and fluoxetine was not as effective as phen–fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen–flu are warranted.

Keywords:

fluoxetine, fenfluramine, phentermine, cardiac valves, weight loss, co-morbidities

Original Article