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Metformin Safer Than Sulfonylureas in Patients With Diabetes and Heart Failure

Studies showed that mono therapy of metformin had 85% fewer deaths and hospitalizations then sulfonylurea.

Metformin therapy is associated with less morbidity than sulfonylurea therapy in patients with diabetes and heart failure,.
"Metformin is considered contraindicated in patients with heart failure because of concerns over lactic acidosis, despite increasing evidence of potential benefit," write Dean T. Eurich, BSP, MSc, from the Institute of Health Economics in Edmonton, Alberta, Canada, and colleagues. "The near absence of any cases of lactic acidosis in large observational studies and the fact that metformin levels do not correlate with lactate levels in individuals who do develop lactic acidosis supports the viewpoint that metformin may be ‘an innocent bystander’ in sick patients rather than a causal agent."

Using the Saskatchewan Health databases, the investigators identified 12,272 new users of oral antidiabetic agents from 1991 through 1996. Of these, 1,833 subjects had incident heart failure, including 208 receiving metformin monotherapy, 773 taking sulfonylurea monotherapy, and 852 taking combination therapy. Differences in all-cause mortality, all-cause hospitalization, and the combination (all-cause hospitalization or mortality) were evaluated with multivariate Cox proportional hazards models.
The average age was 72 years; 57% were male, and average duration of follow-up was 2.5 ± 2.0 years. Compared with sulfonylurea therapy, metformin therapy was associated with fewer deaths (404 [52%] for sulfonylurea monotherapy vs 69 [33%] for metformin monotherapy; hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54 – 0.91; and 263 [31%] for combination therapy [HR, 0.61; 95% CI, 0.52 – 0.72]). There was also a decrease in deaths or hospitalizations: 658 (85%) for sulfonylurea monotherapy vs 160 (77%) for metformin monotherapy (HR, 0.83; 95% CI, 0.70 – 0.99) and 681 (80%) for combination therapy (HR, 0.86; 95% CI, 0.77 – 0.96). Time to first hospitalization was not significantly different between study groups.

"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," the authors write. "Importantly, we also found that metformin exposure was not associated with an increase in hospitalizations, supporting the premise that it appears to be safe in this vulnerable population."
"Conventional wisdom and practice guidelines have created a practice environment where all of the patients in our study who were taking metformin would be considered to be victims of ‘inappropriate’ or ‘unsafe’ prescribing," the authors write. "Whether our findings are sufficiently robust to either liberalize the careful use of metformin in diabetic heart failure patients or simply engender sufficient equipoise to mandate a randomized trial is a question of clinical judgment."

The current retrospective analysis suggests that sulfonylurea therapy is inferior to metformin or combination therapy in preventing mortality among patients with diabetes and heart failure. However, the three diabetes treatment strategies were similar in terms of total hospitalizations, diabetes-related mortality, and cardiovascular mortality.
Diabetes Care. 2005;28:2345-2351

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