Objective There are conflicting reports concerning metformin use and mortality rates in type 2 diabetes mellitus (T2 DM) patients. The aim of this study was to examine the relationship between metformin use and all-cause mortality in veterans with T2 DM.
Research Design and Methods We studied a cohort of 2,186 veterans treated for T2 DM at the VAMC using the CPRS database in the calendar year 2000. All-cause mortality was compared among cohorts of metformin users (n = 1,207) versus non-metformin (n = 999) users on an intention to treat basis. Patients in the metformin cohort were treated with metformin alone or in combination with other antidiabetic drugs. Glyburide was the most commonly used hypoglycemic agent in the cohort of non-metformin users. Univariate and multivariate Cox regression was used to estimate the hazard ratio (HR) of all-cause mortality after adjusting for age, race, insulin use, use of ACEI/ARBs or statins, GFR, and HbA1C.
Results The average length of follow-up in metformin and non-metformin users was 61.7 ± 16.8 and 60.7 ± 17.9 months, respectively. Both groups were similar in age, race, and baseline GFR. Metformin users had higher exposure to insulin, ACEI/ARB, and statins and had higher HbA1C. Crude mortality rates were similar in both groups: 266 (22%) metformin users and 253 (25.3%) non-metformin users died (p = NS). Univariate analysis demonstrated that age (HR 1.051) and insulin exposure (HR 1.34) were independent predictors of decreased months of survival. Race (HR 0.71) and GFR (HR 0.988) had a protective effect. There was a trend for improved survival with metformin use (HR 0.85, p < .07). After multivariate adjustment for age, race, insulin use, baseline GFR, HbA1C, exposure to ACEI/ARBs or statins, metformin users had significantly decreased all-cause mortality compared with the non-metformin users cohort (adjusted HR 0.77 [95% CI 0.64-0.93], p < .0064). In secondary analysis, with patients stratified according to insulin exposure, all-cause mortality remained decreased in metformin users (HR 0.65, p < .037).
Conclusion In this study, treatment of T2 DM with a regimen containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with an antidiabetic regimen without metformin.
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