Practice Update: Diabetes

CONFERENCE COVERAGE 14

Long-TermMetformin Treatment Found to Reduce Risk of Heart Disease in Adults with Type 1 Diabetes Metformin may be an effective long-term strategy worthy of adding to an individual’s diabetes care plan in order to reduce the risk of heart disease in adults with type 1 diabetes. This conclusion, based on results of the Results of the JDRF Reducing with Metformin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL) trial, was presented at the American Diabetes Association’s 77th Scientific Sessions, from June 9–13. J ohn Petrie, MD, PhD, of the University of Glasgow, UK, explained that met- formin is an inexpensive medication REMOVAL studied 428 middle-aged adults with longstanding (average 33 years) type 1 diabetes. white blood cell inhibition, improvement of aspects of endothelial function, and slowed production of advanced glycation end-products.

considered first-line therapy to control glu- cose in individuals with type 2 diabetes. It is also widely used to improve cardiovascular risk in adults with type 2 diabetes. Dr Petrie and colleagues set out to determine whether similar benefits could be expected for people with type 1 diabetes. Metformin may be prescribed for patients with type 1 diabetes who are also overweight, to help control blood sugar and weight, and to allow a lower daily insulin dose. The multicenter, international REMOVAL trial enrolled patients at 23 centers across the UK, Australia, Canada, Denmark, and The Netherlands. Dr Petrie and his team investigated whether 3 years of treatment with metformin reduced heart disease in middle-age adults with type 1 diabetes at increased risk of cardiovascular disease. Ultrasound was used to measure ath- erosclerosis in the carotid arteries as a surrogate marker of heart disease.

Patients harbored three or more risk fac- tors for cardiovascular disease, including body mass index >27 kg/m 2 ; hemoglobin A1C >8.0; known cardio/peripheral vas- cular disease; current smoker; high blood pressure; high cholesterol or triglycerides; strong family history of cardiovascular dis- ease; or duration of diabetes >20 years. Participants were assigned 3 years of oral metformin (two 500 mg tablets titrated up to twice daily); or matching placebo. Metformin reduced the progression of ath- erosclerosis, measured using the Diabetes Control and Complications Trial ultrasound protocol significantly over 3 years and trended toward reduction when measured by the protocol recommended for individ- uals without diabetes. Short-term reduction in hemoglobin A1C meant that glucose did not account for this reduction. Metformin exerts direct effects against atherosclerosis, including

Patients who received metformin lost weight, and their insulin doses were reduced during the study. Hemoglobin A1C levels, however, exhibited reduction during the first 3 months of metformin treat- ment only. Cholesterol was also reduced, though >80% of l participants had been taking stat- ins prior to the trial. Weight reduction and cholesterol lowering may have played a role in reducing atherosclerosis. Estimated glomerular filtration rate by the Modification of Diet in Renal Disease equa- tion rose sharply on initiation of metformin. Dr Petrie asserted, however, that this rise needs to be studied further to determine any clinical significance. Some patients stopped taking metformin because of nausea or abdominal pain. No increase in hypoglycemia risk was observed. Dr Petrie concluded, “A decrease in weight and insulin dose was more or less expected, but we were surprised to dis- cover a reduction in LDL cholesterol and atherosclerosis progression with metformin treatment. Results of REMOVAL support wider prescribing of metformin to help reduce heart disease risk factors over a lifetime of type 1 diabetes, mirroring its use in adults with type 2 diabetes.” He added, “Since our study confirmed that metformin improved blood sugar control only in the very short term, guidelines in the US and UK should be updated to reflect the lack of a sustained effect of metformin on blood glucose levels in adults with type 1 diabetes. So, REMOVAL may result in less prescribing of metformin for blood glucose control in type 1 diabetes.” REMOVAL, with 3 years of follow-up, was one of the longest studies to have been conducted of metformin for type 1 diabetes. Evidence is needed of long-term effects of metformin on cardiovascular events rather than intermediate markers of cardiovascu- lar health. www.practiceupdate.com/c/54539

A decrease in weight and insulin dose was more or less expected, but we were surprised to discover a reduction in LDL cholesterol and atherosclerosis progression with metformin treatment.

PracticeUpdate Editorial team.

© ADA/Rodney White 2017

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