Several studies have demonstrated that excess weight is a major risk factor for diabetes in both men and women, as well as in the adult population as a whole. Even modest weight loss has been shown to significantly reduce the risk of progression from pre-diabetes to diabetes and to lead to better glycemic control,as well as improvements in cardiovascular risk factors such as hypertension and dyslipidemia. Diabetes is itself a major risk factor for hypertension, dyslipidemia and cardiovascular disease, with approximately 65% of diabetes patients dying of cardiovascular or cerebrovascular causes. Current American Diabetes Association (ADA) standards of care give aggressive control of glycemia the same emphasis as control of hypertension and dyslipidemia.

The importance of the standard initial treatment for both obesity and diabetes – lifestyle modification including diet and exercise – has recently been reviewed by the ADA. However, the generally disappointing long-term results of these treatment modalities have led to increased interest in pharmaceutical intervention. Effective medications for maintaining glycemic control in diabetic patients are available. One of the most frequently prescribed in obese diabetic subjects is metformin as, unlike insulin, sulfonylureas or thiazolidinediones, it does not promote weight gain,^15, 16, 17 and further pharmacological weight-loss options are clearly needed.¹⁸

Topiramate, a sulfamate-substituted monosaccharide that is approved worldwide for the adjunctive treatment of specific seizure disorders and for migraine prophylaxis, has been investigated for the treatment of obesity and type 2 diabetes. Topiramate has shown dose-related weight loss in rodent models of obesity and diabetes. A 6-month dose-ranging study in humans likewise found dose-related weight loss. In a study of longer duration, weight loss continued for at least 1 year. In a weight-loss maintenance study,randomized subjects who had lost at least 8% of their enrollment weight during an 8-week low-calorie-diet run-in were given placebo or topiramate. In the topiramate-treated subjects, weight loss continued for 44 weeks, with evidence of stability for 16 weeks thereafter. By contrast, placebo-treated subjects experienced weight regain after week 24.

The present study was carried out to investigate the efficacy and safety of topiramate for weight loss in a population of obese individuals with type 2 diabetes being treated with metformin. Efficacy was evaluated in terms of both weight loss and glycemic parameters.