Long-Term Metformin Drops Risk of Heart Disease in Adults with T1D?

Treatment with metformin may help to reduce long-term heart disease risk in middle-aged adults with type 1 diabetes who are at increased risk for cardiovascular disease (CVD), according to a study presented simultaneously this week at the American Diabetes Association’s 77th Scientific Sessions at the San Diego Convention Center and in T

he Lancet Diabetes & Endocrinology

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A multicenter, international clinical trial, the REMOVAL trial, enrolled patients at 23 centers across the United Kingdom, Australia, Canada, Denmark and the Netherlands and used ultrasound to measure atherosclerosis in the carotid arteries as a surrogate marker of heart disease. Atherosclerosis is a form of hardening of the arteries that is the leading cause of heart attacks, strokes and peripheral vascular disease.

REMOVAL studied 428 middle-aged adults with longstanding type 1 diabetes--on average for 33 years. The patients had 3 or more risk factors for cardiovascular disease, including BMI over 27; A1C greater than 8.0; known CVD/peripheral vascular disease; current smoker; high blood pressure; high cholesterol or triglycerides; strong family history of CVD; or duration of diabetes more than 20 years.

Trial participants were assigned interventions of 3 years duration of either oral metformin treatment or matching placebos.

Patients who received metformin lost weight, and their insulin doses were able to be reduced during the study. However, A1C levels showed reduction only during the first 3 months of metformin treatment. Cholesterol was also reduced, even though more than 80% of trial participants were already taking statins. Weight reduction and lowering of cholesterol may therefore have played a role in reducing atherosclerosis. Estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation was sharply increased on starting metformin, however, the investigators said they believe this needs to be studied further to determine if there is any clinical significance. Some people stopped taking metformin because of nausea or abdominal pain, and there was no increase in the risk of hypoglycemia.

“A decrease in weight and insulin dose was more or less expected, however, we were surprised to discover a reduction in LDL-cholesterol and atherosclerosis progression with metformin treatment,” chief investigator John Petrie, MD, PhD, professor of diabetic medicine at the University of Glasgow in Scotland said in a press release about the results. “The results of REMOVAL support wider prescribing of metformin to help reduce heart disease risk factors over a lifetime of type 1 diabetes, mirroring its current use in adults with type 2 diabetes.”

“Since our study confirmed that metformin only improved blood sugar control in the very short term, guidelines in the U.S. and United Kingdom should be updated to reflect the lack of a sustained effect of metformin on blood glucose levels in adults with type 1 diabetes,” Petrie explained. “So after REMOVAL there may actually be less prescribing in type 1 diabetes for blood glucose control.”

Reference

Petrie JR, Chaturverdi N, Ford I, et al. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Presented at: The American Diabetes Association’s 77th Scientific Sessions, June 9-13, 2017. San Diego.