Decreased Mortality Associated With the Use of Metformin Compared With Sulfonylurea Monotherapy in Type 2 Diabetes

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Abstract
OBJECTIVE—The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents. RESEARCH DESIGN AND METHODS—Saskatchewan Health databases were used to examine population-based mortality rates for new users of oral antidiabetic agents. Individuals with prescriptions for sulfonylurea or metformin in 1991–1996 and no use in the year prior were identified as new users. Prescription records were prospectively followed for 1–9 years; subjects with any insulin use were excluded. Causes of death were identified based on ICD-9 codes in an electronic vital statistics database. Multivariate logistic regression and survival analyses were used to assess the differences in mortality between drug cohorts, after adjusting for potential confounding variables. RESULTS—The total study sample comprised 12,272 new users of oral antidiabetic agents; the average length of follow-up was 5.1 (SD 2.2) years. In subjects with at least 1 year of drug exposure and no insulin use, mortality rates were 750/3,033 (24.7%) for those receiving sulfonylurea monotherapy, 159/1,150 (13.8%) for those receiving metformin monotherapy, and 635/4,683 (13.6%) for those receiving combination therapy over an average 5.1 (SD 2.2) years of follow-up. The adjusted odds ratio (OR) for all-cause mortality for metformin monotherapy was 0.60 (95% CI 0.49–0.74) compared with sulfonylurea monotherapy. Sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR 0.66, 95% CI 0.58–0.75). Reduced cardiovascular-related mortality rates were also observed in metformin users compared with sulfonylurea monotherapy users. CONCLUSIONS—Metformin therapy, alone or in combination with sulfonylurea, was associated with reduced all-cause and cardiovascular mortality compared with sulfonylurea monotherapy among new users of these agents.