Dexfenfluramine treatment of obesity: a double blind trial with post trial follow up

OBJECTIVE: As successful weight management demands a long term approach, a better understanding of weight changes during and for significant periods after cessation of dexfenfluramine therapy is essential to the evaluation of the drug's effectiveness in clinical practice. This study aimed to investigate additional benefits to weight loss during 6 months treatment with dexfenfluramine in 60 patients enrolled in a weight loss programme. DESIGN: Sixty obese subjects (21 males; 39 females) were randomised to dexfenfluramine (15 mg twice daily) or placebo for six months. Fifty one (27 dexfenfluramine; 24 placebo) subjects completed the double blind, randomised, placebo controlled clinical trial. RESULTS: After a one month 'run in' phase and six months treatment, weight loss in the dexfenfluramine group was significantly greater than placebo, 9.7 +/- 1.1 kg vs 4.9 +/- 0.9 kg (mean +/- s.e.m.); P = 0.002. Reduction in body fat, 5.0 +/- 0.7 kg vs 1.0 +/- 0.9 kg; P = 0.002 and waist circumference, 10.5 +/- 1.9 cm vs 5.7 +/- 1.1 cm; P = 0.04 was also greater in the dexfenfluramine group. Despite significant weight loss, waist to hip ratio (WHR) did not change in either group. The dexfenfluramine group reported a significantly greater incidence of nausea, dry mouth and dizziness which tended to decrease as treatment progressed. No subjects withdrew due to drug induced side effects. Reduction in serum triglyceride levels and an increase in HDL cholesterol (in female subjects) in conjunction with a reduction in fasting insulin, collectively support an improved cardiovascular risk profile in the dexfenfluramine group. Despite significant weight loss, these risk factor measurements worsened in the placebo group. After cessation of dexfenfluramine therapy, there was a significantly greater weight regain indicating a loss of treatment effect. By 5 months after cessation of dexfenfluramine, the treatment effect was negated with weight loss in the dexfenfluramine (6.0 +/- 1.6 kg) and placebo (6.2 +/- 1.3 kg) group, similar. CONCLUSION: The results of this study support the longer term use of dexfenfluramine therapy for patients with chronic obesity.