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IS THE COMBINATION OF SULFONYLUREAS AND METFORMIN ASSOCIATED WITH AN INCREASED RISK OF CARDIOVASCULAR DISEASE OR ALL-CAUSE MORTALITY? A Meta-Analysis of Observational Studies

From the Department of Medicine, Tulane University School of Medicine (AR, VAF), the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine (NK, KR), New Orleans, Louisiana, USA, and Southern California Permanente Medical Group (KR), Pasadena, California

vfonseca{at}tulane.edu

ABSTRACT

Background: Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results.

Objective: To evaluate the effects of combination therapy of sulfonylureas and metformin on risk of all-cause mortality and cardiovascular disease among people with type 2 diabetes.

Research Design and Methods: A MEDLINE search (1966- July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of cardiovascular disease or all-cause mortality. From 299 relevant reports, nine were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of cardiovascular disease and/or mortality was reported, adjusted relative risk or equivalent (hazard ratio, odds ratio), and corresponding variance or equivalent was reported.

Results: The pooled relative risks (95% confidence intervals) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for cardiovascular disease mortality, and 1.43 (1.10-1.85) for a composite endpoint of cardiovascular disease hospitalizations or mortality (fatal or non-fatal events).

Conclusions: The combination therapy of metformin and sulfonylurea significantly increased the relative risk of the composite endpoint of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either cardiovascular disease mortality or all-cause mortality alone.

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