Diabetes-Free Hearts Not Helped by Metformin

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Metformin in patients without diabetes did not improve cardiovascular risk

November 7, 2013 / Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

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(dailyRx News) The most widely prescribed medication for diabetes, metformin, also has heart health benefits for diabetes patients. For those without diabetes, however, its effects on the heart may be limited.

Known as a safe, inexpensive medication for lowering blood sugar, metformin has been shown to provide an added perk — lowering cardiovascular risks in patients with diabetes.

In a new report, however, scientists observed that metformin may not improve heart disease results for those without diabetes.

"Talk to a doctor about medications that are best for atherosclerosis."

David Preiss, PhD, clinical senior lecturer in metabolic medicine at BHF Glasgow Cardiovascular Research Center at the University of Glasgow in Scotland, and his colleagues analyzed results of 173 individuals who did not have diabetes but were being treated for heart disease with cholesterol-lowering statins. The study was called The Carotid Atherosclerosis: MEtformin for insulin ResistAnce (CAMERA) trial.

In a previous 20-year investigation involving more than 5,000 type 2 diabetes patients, called the United Kingdom Prospective Diabetes Study, scientists had discovered that the risk for heart attack in diabetes patients was reduced by 39 percent in 10 years for those taking metformin (brand names Glucophage, Glucophage XR, Glumetza, Fortamet and Riomet). Dr. Preiss and his team set out to find if those without diabetes would have similar cardiovascular benefits.

For 18 months, 86 patients received 850 milligrams of metformin, twice daily, while 87 received a matching placebo (fake medication).

After a year and half of treatment, the researchers looked at a measure of artery thickness called carotid intima-media thickness (cIMT). They gauged the thickness of the inner two layers of the carotid arteries (the intima and media). Thickening of the arteries is a sign of atherosclerosis.

The two carotid arteries are the blood vessels that carry blood through the neck to the brain.

In the metformin group, there was no improvement in cIMT or the extent of atherosclerotic plaque in the carotid arteries.  In fact, the average cIMT increased significantly in both groups (0.024 mm per year in the metformin group and 0.017 mm in the placebo group).

The researchers noted 136 adverse events in 63 patients taking metformin and 115 in 58 patients given placebo. Patients taking metformin were more likely to have gastrointestinal events (diarrhea, nausea and vomiting).

Metformin appeared to have an effect on fat loss. Overall, measures of body weight, body fat, body mass index (BMI) and waist circumference significantly dropped in the metformin group. Metformin patients lost an average of six and a half pounds at the end of 18 months.

"This was a study designed to see if using a blood sugar lowering medication called metformin would decrease the development of a condition called atherosclerosis in the carotid arteries of non-diabetic individuals.  The study concluded that metformin did not reduce the development of atherosclerosis in these non-diabetic individuals," explained Mohan Sathyamoorthy, MD, Chief of the Cardiovascular Division at Baylor All Saints Medical Center.

"The key takeaway is that other established methods for reducing the risk of development of atherosclerosis, such as avoidance of smoking, heart healthy diet and exercise commitment, and use of medications such as statins to treat high cholesterol when diet and exercise are not sufficient, are key ways to prevent atherosclerotic vascular disease," said Dr. Sathyamoorthy.

“Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population [those without diabetes but with heart disease],” the authors of this study concluded.

Dr. Preiss told dailyRx News, “To summarize the results of the CAMERA study, it showed that giving metformin to patients already on statins with heart disease but without diabetes appeared to have little impact on important markers of heart attack risk. However, metformin led to weight loss, which is in keeping with its ability to reduce the chance of developing diabetes."

"The next step is to conduct a large study to conclusively determine whether metformin may reduce risk of heart attacks, and such a trial is in its early stages. This trial will also address whether metformin can reduce the risk of developing cancer, something that some small studies have suggested but that remains unproven,” Dr. Preiss said.

This study was published online November 7 in The Lancet Diabetes & Endocrinology. Funding was provided by the Chief Scientist Office (Scotland).