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

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/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.