Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients

Aim: In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods: From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m² and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results: A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 ± 1.8 kg and -6.6 ± 1.1 kg) and also with rosiglitazone (-11.0 ± 1.9 kg and -7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p <0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 μU/ml, p <0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p <0.005) with a concomitant decrease in β-cell function as measured by HOMA of β-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p <0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion: Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.