Hypoglycaemic therapy in type 2 diabetes. Part I. Metformin is the only glucose-lowering drug known to prevent complications of diabetes

Metformin monotherapy appears to reduce mortality in patients with type 2 diabetes, with generally acceptable adverse effects. To determine whether any other glucose-lowering drugs have been shown to prevent or delay the onset of long-term clinical complications of diabetes, we conducted a systematic review of the literature using the standard Prescrire methodology. We identified only six randomised controlled trials, versus placebo or no treatment, that were designed to evaluate the efficacy of glucose-lowering drugs in preventing the clinical complications of type 2 diabetes. Three trials of various insulins failed to demonstrate a tangible benefit for patients with type 2 diabetes and moderate hyperglycaemia. In one trial, cardiovascular mortality appeared to be higher in the group treated with tolbutamide, a glucose-lowering sulphonylurea. In a trial lasting 11 years, another sulphonylurea, glibenclamide, appeared to reduce the incidence of diabetes complications, but it had no impact on mortality. The results of this trial are undermined by methodological flaws. In trials lasting up to 3 years, pioglitazone, alogliptin and saxagliptin had no effect in preventing the clinical complications of diabetes in patients with relatively high blood glucose levels. * In 2014, metformin is the only hypo- glycaemic drug that appears to reduce mortality among patients with type 2 diabetes in comparative trials. Compa- rative data suggesting that gliben- clamide prevents some complications of diabetes are rather unconvincing. No other glucose-lowering drugs have been shown to prevent the complica- tions of diabetes, but their evaluation is inadequate.