Oral glucose-lowering drugs affect cardiovascular risk differently

Sulfonylureas are associated with an increase in the risk of cardiovascular disease compared with metformin in patients with type 2 diabetes, according to the results of a Danish nationwide analysis.

The findings were presented by Tina Ken Schramm, MD, lead investigator of the study and a research fellow in the Department of Cardiology at Gentofte University Hospital, Hellerup, Denmark.

The effect of oral glucose-lowering medications on cardiovascular risk entered the spotlight with the publication of controversial studies that suggested an increase in the incidence of myocardial infarction (MI) and heart failure in patients taking rosiglitazone, a thiazolidinedione.

For the Danish analysis, investigators followed 110,913 residents older than 20 years without a prior MI who initiated monotherapy with an oral glucose-lowering drug from 1997 to 2006. The use of specific oral glucose-lowering drugs was identified by claimed prescriptions. Patients were followed for a maximum of 9 years. Over that time, 6,598 suffered a cardiovascular death.

When compared with metformin as a single treatment, all sulfonylurea drugs examined, except for gliclazide (not marketed in the United States), had hazard ratios for cardiovascular death in excess of 1.0 on multivariate analysis, all of which achieved statistical significance. (Metformin was chosen as the reference drug because of studies showing it to be associated with a decrease in the risk of death in the United Kingdom Prospective Diabetes Study [UKPDS] of patients with type 2 diabetes.) The sulfonylurea drugs associated with an increase in cardiovascular mortality were glimepride, glibenclamide, glipizide, and tolbutamide.

Among the nonsulfonylureas assessed, insulin was associated with a significant excess in cardiovascular hazard, and repaglinide and acarbose had risks similar to metformin.

"Results of this study should be examined in conjunction with other studies, in particular the UKPDS study, for the combined reasons that we believe that metformin, in general, should be part of the treatment in type 2 diabetes to reduce cardiovascular mortality, but gliclazide and repaglinide may be good alternatives," says Dr. Schramm.