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

Author: Whigham LD, Dhurandhar NV, Rahko PS, Atkinson RL

Author affiliation: 1Departments of Medicine and Nutritional Sciences, University of Wisconsin, Madison, WI, USA.

Publication date & source: 2006.12.05, Int J Obes (Lond)., [Epub ahead of print]

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+/-0.6% of baseline weight and phen-flu patients lost 9.0+/-0.6% (P<0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.4+/-0.6 vs 13.3+/-0.9%). LOCF decreases in body mass index (BMI) at 6 months were -5.3 and -3.6 kg/m(2) for phen-fen and phen-flu, respectively (P<0.001), and 6.2+/-0.3 vs 5.4+/-0.4 kg/m(2), 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.International Journal of Obesity advance online publication, 5 December 2006; doi:10.1038/sj.ijo.0803498.