Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes


Dr Jeffrey A. Johnson, #1200, 10405 Jasper Ave, Edmonton, AB, Canada T5J 3 N4. e-mail:


Aim  Metformin therapy reduces microvascular complications in Type 2 diabetes; questions remain, however, regarding its impact on macrovascular events. This study examined metformin use in relation to risk of cardiovascular-related hospitalization and mortality.

Methods  We conducted a retrospective cohort analysis, using Saskatchewan Health administrative databases to identify new users of oral antidiabetic drugs. Subject groups were defined by medication use during 1991–1999: sulphonylurea monotherapy, metformin monotherapy, or combination therapy. Deaths and non-fatal hospitalizations recorded during the study period were identified as cardiovascular-related from ICD-9 codes. The main outcome was a composite of first non-fatal hospitalization or death. Standard multivariate techniques, including propensity scores, were used to adjust for potential confounding. Multivariate Cox proportional hazard models were used to examine the relationship between metformin use and the composite endpoint.

Results  Metformin monotherapy was associated with a lower risk of the composite endpoint (adjusted hazard ratio 0.81; 95% confidence interval 0.68, 0.97) compared with sulphonylurea monotherapy. Combination therapy with meformin and a sulphonylurea was associated with lower mortality, but had similar hospitalization rates, to sulphonylurea monotherapy.

Conclusions  Metformin monotherapy was associated with a lower risk of cardiovascular-related morbidity and mortality, and combination metformin and sulphonylurea therapy was associated with a reduced risk of fatal cardiovascular events, when compared with sulphonylurea monotherapy.