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Publication Briefs

Comparative Effectiveness Study Compares Cardiovascular Outcomes for Two Common Anti-Diabetes Drugs among Veterans

Cardiovascular disease (CVD) accounts for most deaths in patients with diabetes mellitus. Randomized trials have evaluated CVD risk associated with selected thresholds of glycemic control, but how specific anti-diabetic drugs contribute to CVD is less clear. This study compared CVD outcomes and all-cause mortality in a cohort of Veterans (n=253,690) who received regular VA healthcare and were prescribed metformin or sulfonylureas — the two most commonly used anti-diabetic drugs. Compared with metformin, sulfonylureas are associated with increases in weight and lipid levels, as well as greater risk for hypoglycemia, but similar glycemic control. Thus, metformin is recommended as first-line therapy for patients without contraindications. However, sulfonylureas are sometimes preferred because they require little titration and have fewer gastrointestinal adverse effects. Using VA data which was linked to Centers for Medicaid and Medicare Services data, investigators identified Veterans who initiated oral monotherapy with either metformin (n=155,025) or sulfonylureas (n=98,665) between 10/01 and 9/08. Investigators then assessed hospitalization for acute myocardial infarction (AMI) or stroke, or death, adjusting for clinical and demographic covariates (e.g., blood pressure, LDL cholesterol, BMI, serum creatinine, and HBA1c); healthcare use (e.g., number of outpatient visits, active medications, hospitalization); smoking status; medications indicative of CVD; and comorbid conditions (e.g., heart disease, asthma, COPD).


  • This study shows a modest but clinically important 21% increased risk of hospitalization for AMI or stroke, or death from any cause associated with the initiation of sulfonylurea compared with metformin therapy.
  • The sulfonylurea group had higher rates of hospitalizations and deaths due to cardiovascular disease: 18.2 per 1,000 person years for those taking a sulfonylurea and 10.4 per 1,000 person years for those taking metformin.
  • These findings suggest that for 1,000 patients who are initiating treatment for diabetes using metformin rather than sulfonylureas, there are 2 fewer heart attacks, strokes, or deaths per year of treatment.
  • The findings do not clarify whether the difference in CVD risk is due to harm from sulfonylureas, benefit from metformin, or both.


  • Confounding could occur if Veterans with certain characteristics that increase CVD risk also were more likely to use metformin or sulfonylureas.
  • If Veterans were admitted to non-VA facilities for study outcomes, those events could be missed and outcome misclassification could occur.

Dr. Roumie was supported by an HSR&D Career Development Award and is part of the GRECC (Geriatric Research Education Clinical Center) at VA Tennessee Valley Healthcare System.

PubMed Logo Roumie C, Hung A, Greevy R, et al. Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study. Annals of Internal Medicine November 6, 2012;157(9):601-610.

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HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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