Preamble
After having analysed data on the harm-benefit balance of metformin as initial therapy for type 2 diabetes (Prescrire Int n° 154), we will now examine alternative glucose-lowering drugs when metformin is unsuitable or fails to control blood glucose levels. In the first part of this review, we will analyse data on the efficacy of glucose-lowering drugs in preventing the clinical complications of type 2 diabetes. In a coming issue, we will compare the adverse effect profiles of available glucose-lowering drugs, and their impact on surrogate endpoints such as HbA1c.

Abstract

• 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 hypoglycaemic drug that appears to reduce mortality among patients with type 2 diabetes in comparative trials. Comparative data suggesting that glibenclamide prevents some complications of diabetes are rather unconvincing. No other glucose-lowering drugs have been shown to prevent the complications of diabetes, but their evaluation is inadequate.

 ©Prescrire 1 April 2015

"Hypoglycaemic therapy in type 2 diabetes. Part I. Metformin is the only glucose-lowering drug known to prevent complications of diabetes" Prescrire Int 2015; 24 (159): 103-106. (Pdf, subscribers only)