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Metformin Observed to Reduce Heart Disease Risk in Type 1 Diabetes

REMOVAL trial results presented at the American Diabetes Association’s 77th Scientific Sessions.
Published Online: Jun 12,2017
Laurie Toich, Assistant Editor
According to findings from the REMOVAL trial, metformin may be an effective long-term treatment to reduce the risk of heart disease among patients with type 1 diabetes. The results were presented at the American Diabetes Association’s 77th Scientific Sessions.
 
Metformin is a first-line treatment to achieve glucose control in patients with type 2 diabetes. It is also commonly used to reduce cardiovascular risks for these patients. Metformin can directly prevent atherosclerosis by inhibiting the function of white blood cells, improving endothelial function, and slowing the production of advanced glycation end-products, according to the session.
 
In the study, the investigators examined whether metformin could elicit similar effects in patients with type 1 diabetes. For these patients, metformin may be prescribed to those who are overweight to control blood glucose levels and weight. Metformin can result in a lower insulin dose for patients with type 1 diabetes, according to the session.
 
The investigators explored whether 3 years of treatment with metformin would reduce the risk of heart disease risk among 428 middle-aged patients with type 1 diabetes who are at risk of heart disease. They used ultrasound to measure atherosclerosis in the carotid arteries to determine heart disease.
 
All patients included had long-term diabetes and 3 or more cardiovascular disease risk factors, such as body mass index over 27, A1C greater than 8, known heart disease, smoking, high blood pressure, high cholesterol/triglycerides, family history of cardiovascular disease, or diabetes duration longer than 20 years, according to the session.
 
Patients were assigned to receive oral metformin or matching placebo.
 
The investigators found that progression of atherosclerosis was reduced over 3 years among patients treated with metformin. Since there was only a short-term reduction in A1C, improved glucose control was not able to elicit this effect, according to the session. The reduction in A1C was only observed for the first 3 months of treatment.
 
Patients treated with metformin were also observed to lose weight and have their insulin doses reduced over the course of the study. Although 80% of patients were taking statins, those taking metformin observed reductions in cholesterol. The researchers believe that these factors played a role in reducing atherosclerosis.
 
The estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation was observed to increase for patients starting metformin, but the investigators believe this finding needs to be studied further to determine the significance, according to the session.
 
“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,” said chief investigator John Petrie, MD, PhD. “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.”
 
The REMOVAL study is one of the longest trials to explore the use of metformin among patients with type 1 diabetes. Evidence about the long-term effects of metformin on cardiovascular health is needed, according to the session.
 
“Since our study confirmed that metformin only improved blood sugar control in the very short term, guidelines in the US 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,” Dr Petrie said. “So, after REMOVAL there may actually be less prescribing in type 1 diabetes for blood glucose control.”