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.


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.
Eurich
Dean T
DT
Institute of Health Economics, Edmonton, Alberta, Canada.
Majumdar
Sumit R
SR
McAlister
Finlay A
FA
Tsuyuki
Ross T
RT
Johnson
Jeffrey A
JA
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009017:Morbidity; D012525:Saskatchewan / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D008687:Metformin