Background
The comparative effectiveness of sulfonylureas and metformin on cardiovascular disease (CVD) outcomes in type 2 diabetes are not well characterized.
Objective
To compare the effectiveness of sulfonylureas and metformin on the outcome of CVD (acute myocardial infarction, stroke) or death
Design
Retrospective cohort study
Setting
National Veterans Health Administration (VHA) databases linked to Medicare files
Patients
Veterans who initiated metformin or sulfonylureas for diabetes. Patients with chronic kidney disease or serious medical illness were excluded.
Measurements
Composite outcome of hospitalizations for acute myocardial infarction, stroke, or death. Cox regression analyses compared the incidence of the composite outcome between groups, adjusting for baseline demographics, medications, cholesterol, glycated hemoglobin, creatinine, blood pressure, body mass index, healthcare utilization and co-morbidities.
Results
Among 253,690 patients (98,665 sulfonylurea and 155,025 metformin initiators) the crude outcome rates were 18.2 and 10.4 per 1000 person-years in sulfonylurea and metformin users, respectively (adjusted hazard ratio [aHR] 1.21, 95% Confidence Intervals [CI] 1.13, 1.30). Results were consistent for both glyburide (aHR 1.26, 95% CI 1.16, 1.37) and glipizide (aHR 1.15, 95% CI 1.06, 1.26) as well as for those with prior history of CVD (aHR 1.25, 95% CI 1.13, 1.55) and without history of CVD (aHR: 1.16, 95% CI: 1.06, 1.29). Results were also consistent in a propensity score-matched analysis. For patients initiating sulfonylureas rather than metformin, we estimated an excess of 1 and 4 CVD events per 1000 person-years for those without and with a CVD history, respectively.
Limitations
Data on women and minorities is limited but reflective of the VHA population.
Conclusions
Use of sulfonylureas compared to metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death.
