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06-04-2011 | Diabetes | Article

Adverse outcome risk lower with metformin than other hypoglycemic agents


Free abstract

MedWire News: The risk for death and cardiovascular (CV) disease is lower among people with Type 2 diabetes treated with metformin monotherapy than with other commonly used insulin secretagogues (ISs), study results indicate.

Specifically, patients receiving glimepiride, glibenclamide, glipizide, or tolbutamide monotherapy have an all-cause mortality risk at least 20% higher than that of metformin-treated patients, irrespective of having a history of myocardial infarction (MI), the researchers report.

They emphasize, however, that this finding does not mean that these drugs cause harm, but rather that they are less effective at preventing adverse events than metformin.

"Previous studies have shown that ISs, in particular sulphonylureas, are associated with a reduction in long-term [CV] risk. Therefore, the increased risk from ISs shown in our study presumably has more to do with the beneficial effects of metformin," explained Tina Schramm (Copenhagen University Hospital, Denmark) and colleagues.

The findings, obtained from a study involving 107,806 Danish patients with diabetes (9607 with previous MI) aged over 20 years and followed-up for a median of 3.3 years, showed that compared with metformin monotherapy, glimepiride was associated with a 32% increase in all-cause mortality risk among diabetic patients without previous MI.

Furthermore, treatment with glibenclamide, glipizide, and tolbutamide alone resulted in 19%, 27%, and 28% higher respective risks for all-cause mortality than metformin in MI-free patients.

Even when patients with a history of MI were assessed, a similar trend was observed, with 30% to 53% higher all-cause mortality risks associated with monotherapy with these ISs compared with metformin.

Schramm and team report in the European Heart Journal, that the risk for CV death and the composite outcome of MI, stroke, or CV death among the cohort, followed a similar trend to that observed for all-cause mortality risk.

Of note, patients treated with the sulphonylureas gliclazide and repaglinide did not have a significantly increased risk for all-cause or CV mortality.

Editorialists Odette Gore and Darren McGuire (University of Texas Southwestern Medical Center, Dallas, USA) wrote: "With the global prevalence of Type 2 diabetes mellitus increasing rampantly, it has never been more critical to understand the CV efficacy and safety of individual glucose-lowering medication."

Schramm and team conclude: "The notion that individual ISs can exhibit clinically important differences in their safety profile warrants further studies."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Lauretta Ihonor