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Metformin plays role in reducing MI, heart failure risk
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NASHVILLE, Tenn. — Even slight weight effects associated with metformin use may reduce risk for myocardial infarction and heart failure, according to a presenter here.
“We don’t know how metformin works, but I would speculate that suppression of appetite and promotion of weight loss may play a role,” John M. Miles, MD, professor of medicine at the University of Kansas in Kansas City, said during a presentation at the AACE 24th Annual Scientific & Clinical Congress.
According to Miles, metformin’s role in reducing MI was established in the original United Kingdom Prospective Diabetes Study, which found a nearly one-third reduction in MI in patients assigned metformin compared with a nonsignificant reduction among those assigned insulin plus a sulfonylurea.
In the 20-year follow-up study, the two groups saw a nearly identical effect on HbA1c, but the insulin plus sulfonylurea group showed a 15% reduction in MI while the metformin group had a “statinesque” 39% event reduction, Miles said.
“What was dramatically different [between the study groups] was body weight, which was greater than control in the sulfonylurea-insulin group, but not greater than control in the metformin group,” Miles said. “Modest intentional weight loss of just a few pounds is associated with longer life in people with type 2 diabetes.”
Miles cited studies showing an association between metformin use and lower risk for heart failure as well. In contrast, other studies suggested an increased risk for heart failure and elevated blood pressure with insulin use.
“If your patient gains 7 kg or 8 kg, should you be surprised that their BP might go up?” he asked.
Miles also said metformin use could safely be expanded to patients with stage 3 kidney disease. Evidence of the drug’s safety in patients with estimated glomerular filtration rates between 30 mL/min/1.73 m2 and 59 mL/min/1.73 m2 comes primarily from retrospective and observational studies, according to Miles. At least one of these showed lower rates of infection, acidosis and all-cause mortality among patients assigned metformin than compared with those not assigned metformin, he said.
In addition, many patients with stage 3 kidney disease are already assigned metformin because their creatinine levels are not in the range that would disqualify them from receiving the medication, according to Miles.
“I would argue that metformin is substantially safe in patients with CKD stage 3, but we need a way to prescribe it with confidence. … We need more pharmacokinetic data in patients with eGFRs between 30 [mL/min/1.73 m2] and 59 [mL/min/1.73 m2],” Miles said. “One of the intriguing possibilities … is that metformin is not only clearly safe in patients with heart failure, but may actually benefit heart failure. We don’t know why, but maybe a reduction in sympathetic activity is a factor.” – by Jill Rollet
Reference:
Miles JM. Oral presentation SGS3. Presented at: AACE 24th Annual Scientific & Clinical Congress; May 13-17, 2015; Nashville, Tenn.
Disclosure: Miles reports no relevant financial disclosures.
Perspective
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George Grunberger, MD, FACP, FACE
Hopefully, this means that clinicians will be able to prescribe metformin more safely and feel more confident doing so. Most of us in the field know that the current restrictions make no sense. Most of us know that there is a potential cardiovascular benefit with metformin, and there is no obvious downside in using in people with moderate renal dysfunction. A lot of people who are not using metformin could benefit because CV problems are the leading cause of morbidity and mortality in these patients.
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