Contraindicated metformin fares well in heart failure patients with diabetes

In an observational study of patients with type 2 diabetes being treated for heart failure, researchers found that metformin-whether used alone in vulnerable patients or in combination-is associated with lower mortality, less morbidity, and fewer hospitalizations compared with sulfonylurea monotherapy. The study, conducted in Canada, was published in Diabetes Care.

Despite a lack of high-quality evidence to refute the researchers' findings, metformin is currently considered contraindicated in patients with heart failure and type 2 diabetes because of concerns over lactic acidosis.

"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, led by Dean T. Eurich, BSP, MSC, stated. "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."

Fewer deaths occurred in subjects using metformin: 404 (52%) for sulfonylurea monotherapy versus 69 (33%) for metformin therapy (HR, 0.70; 95% CI, 0.54–0.91) and 263 (31%) for combination therapy (HR, 0.61; 95% CI, 0.52–0.72).

Also observed was a reduction in deaths or hospitalizations: 658 (85%) for sulfonylurea monotherapy versus 160 (77%) for metformin monotherapy (HR, 0.83; 95% CI, 0.70–0.9) and 681 (80%) for combination therapy (HR, 0.86; 95% CI, 0.77–0.96).

"Some medications that are currently considered contraindicated may have been defined as such on the basis of little or no evidence beyond pathophysiological rationale," the researchers stated. "Since this rationale alone is considered insufficient evidence for
efficacy, it should also be insufficient to declare harm."

The strengths of their study, according to the authors, include the large unselected population-based sample of subjects with heart failure and type 2 diabetes, the comprehensiveness and quality of the databases used, the relatively long duration of follow-up, and the ability to control for the effects of comorbidities and drug therapies known to affect outcomes in patients with heart failure.

One limitation was the lack of access to data on subjects' glycemic control, according to the authors. Another was a possible selection bias due to the chance that physicians may have withheld metformin in subjects perceived to be at an increased risk of adverse events or death. And lastly, the researchers did not have any clinical or laboratory information on factors such as functional status, severity of heart failure, left ventricular function, or renal failure.

SOURCE Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28: 2345–2351.