Improved Clinical Outcomes Associated With Metformin in Patients With Diabetes and Heart Failure

OBJECTIVE:--Metformin is considered contraindicated in patients with heart failure because of concerns over lactic acidosis, despite increasing evidence of potential benefit. The aim of this study was to evaluate the association between metformin and clinical outcomes in patients with heart failure and type 2 diabetes. RESEARCH DESIGN AND METHODS--Using the Saskatchewan Health databases, 12,272 new users of oral antidiabetic agents were identified between the years 1991 and 1996. Subjects with incident heart failure (n = 1,833) were identified through administrative records based on ICD-9 code 428 and grouped according to antidiabetic therapy: metformin monotherapy (n = 208), sulfonylurea monotherapy (n = 773), or combination therapy (n = 852). Multivariate Cox proportional hazards models were used to assess differences in all-cause mortality, all-cause hospitalization, and the combination (i.e., all-cause hospitalization or mortality). RESULTS:--Average age of subjects was 72 years, 57% were male, and average follow-up was 2.5 ± 2.0 (SD) years. Compared with sulfonylurea therapy, fewer deaths occurred in subjects receiving metformin: 404 (52%) for sulfonylurea monotherapy versus 69 (33%) for metformin monotherapy (hazard ratio [HR] 0.70 [95% CI 0.54-0.91]) and 263 (31%) for combination therapy (0.61 [0.52-0.72]). A reduction in deaths or hospitalizations was also observed: 658 (85%) for sulfonylurea monotherapy versus 160 (77%) for metformin monotherapy (0.83 [0.70-0.99]) and 681 (80%) for combination therapy (0.86 [0.77-0.96]). There was no difference in time to first hospitalization between study groups. CONCLUSIONS:--Metformin, alone or in combination, in subjects with heart failure and type 2 diabetes was associated with lower morbidity and mortality compared with sulfonylurea monotherapy.