Metformin Benefits Diabetics with Heart Failure

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Patients with both heart failure and type 2 diabetes who are treated with a metformin-based strategy have a lower mortality risk than matched individuals not treated with anti-diabetic drugs, new findings suggest.

“Our findings bolster prior observational studies demonstrating that diabetic heart failure patients using metformin have better outcomes,” said Finlay A. McAlister, MD, Associate Professor of Medicine and Director of the Epidemiology Coordinating and Research  (Epicore) Center at the University of Alberta in Calgary. “Until evidence from randomized trials becomes available, we believe that metformin-based strategies should be used for glucose lowering in patients with diabetes and heart failure.”

The findings are based on data from a large general practice registry often used in studies examining the use of prescription drugs.

Diabetes is a common co-morbidity in patients with heart failure, but however optimal treatment for type 2 diabetes in individuals with heart failure has not been determined.

Heart failure patients have typically been excluded from studies of glucose-lowering therapies, and the safety of antidiabetic agents in heart failure patients is largely unknown.

In the absence of randomized trials in patients with diabetes and concurrent heart failure, the safety of antidiabetic agents in this population has been based on observational data.  While several observational studies have reported prognostic differences between various antidiabetic agents when used in patients with diabetes and heart failure, these studies routinely involved comparisons between patients receiving active drug therapy and typically lacked a non-drug comparator group. As a result, it has not been possible to categorically determine whether the observed intra-drug differences occurred because one of the drug classes was harmful or because the comparator drug was beneficial.

Dr. McAlister and his colleagues conducted a case-control study using data from the well-validated prospective United Kingdom General Practice Research Database (GPRD) cohort, in which the patient's primary care physician made diagnoses. The GPRD is known for hits high-quality information on co-morbidities and therapy.

The analysis included 1,633 patients 35 years of age or older who were diagnosed with both heart failure and diabetes after January 1988 and who died before October 2007 and 1,633 controls matched for age, sex, clinic site, calendar year, and duration of follow-up. 

Compared with patients not exposed to antidiabetic drugs, metformin users had a 34% lower mortality risk even after controlling for other potential prognostic indicator factors including glycemic control, renal function, BMI, and BP.

Conversely, the use of ACE inhibitors, angiotensin receptor blockers, and beta blockers was associated with reduced mortality.

“By including heart failure patients with diabetes who were not exposed to antidiabetic drugs (a subgroup previously demonstrated to have better glycemic control and less disease burden than those treated with antidiabetic therapies in the UK), we have advanced the evidence base since our results suggest that metformin's apparent benefit over other antidiabetic agents is due to its reduced mortality risk rather than harm with other agents,” Dr. McAlister said.

Finally, he emphasized that while the study used prospectively collected data and was thus free of recall bias, limitations exist. For example, the analysis relied on information obtained from the database on physician diagnoses and documentation of heart failure but did not have independent confirmation of the diagnoses or any data on left ventricular ejection fraction.

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