Obese patients with type 2 diabetes poorly controlled by insulin and metformin: effects of adjunctive dexfenfluramine therapy on glycaemic control

Abstract

Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain.