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Study of Diabetes Drugs Shows Metformin Best at Reducing Risk of Death from Heart Disease

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Study of Diabetes Drugs Shows Metformin Best at Reducing Risk of Death from Heart Disease
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A meta-analysis of 204 studies published in the Annals of Internal Medicine indicated that metformin, the most frequently prescribed drug for patients with type 2 diabetes, reduces by 30 to 40 percent the risk of death from heart disease compared to sulfonylurea drugs, its closest competitor.

The study, “Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis, evaluated the comparative effectiveness and safety of the 12 drugs approved by the FDA to lower blood sugar levels in patients with type 2 diabetes (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium–glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists).

According to Nisa Maruthur, M.D., MHS, lead author of the study and assistant professor of medicine at the Johns Hopkins University School of Medicine, heart attacks and strokes are major risks for individuals who have uncontrolled blood sugar; however, it remains unclear if one drug for diabetes is better than another at lowering the risk of these cardiovascular complications.

The results of the meta-analysis showed that cardiovascular mortality was lower in patients receiving metformin compared to those receiving sulfonylureas. Moreover, reductions in hemoglobin A1c values (a measure of the average blood glucose levels) were similar across monotherapies and metformin-based combinations, except that DPP-4 inhibitors had smaller effects.

“Metformin looks like a clear winner,” Maruthur said in a recent press release. “This is likely the biggest bit of evidence to guide treatment of type 2 diabetes for the next two to three years.”

In the study, researchers looked at cardiovascular disease but also other drug effects, such as glucose control, and common side effects including weight gain, hypoglycemia and gastrointestinal problems. The results showed that body weight was reduced or maintained with metformin, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors; while it increased with sulfonylureas, thiazolidinediones, and insulin. Furthermore, hypoglycemia was more frequent with sulfonylureas, and gastrointestinal adverse events were highest with metformin and GLP-1 receptor agonists. Genital mycotic infections were increased with SGLT-2 inhibitors.

As most patients with type 2 diabetes end up needing more than one blood sugar-lowering drug, the team also investigated how the drugs performed when used as a monotherapy or in combination with other drugs.

The findings suggested that metformin works in a similar manner to sulfonylureas, and the results were consistent with the current recommendation of metformin as a first-line treatment. However, as Maruthur noted, the real question arises when doctors and patients must decide for a second drug to be used in combination with metformin.

“The medications all have different benefits and side effects, so the choice of second-line medications must be based on an individual patient’s preferences,” Maruthur said.

Alongside with the study, the research team also wrote a report for the Agency for Healthcare Research and Quality, which details the studies included in the meta-analysis. These publications will serve as an update in the guidelines of the American College of Physicians and the U.S. Department of Veterans Affairs.

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