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ADA Spotlight: Should Metformin Remain The First-Line Therapy For Type 2 Diabetes?

Should metformin remain first-line therapy for type 2 diabetes? It was one of the more light-hearted but hotly-debated presentations at this year’s 78th Scientific Sessions of the American Diabetes Association (ADA).

The ADA meeting is one of the largest scientific meetings where thousands of healthcare professionals, researchers, and doctors convene to discuss the latest research in diabetes treatment annually.
Currently, the practice is to prescribe metformin as a first-line treatment for those with type 2 diabetes. It has a long history, having been used for over 20 years, and a proven safety and efficacy profile.

Newer drugs, however, have been abounding on the market, namely Jardiance (SGLT2 inhibitors), Invokana (canagliflozin), dipeptidyl peptidase-4 (DPP-4) inhibitors, and Victoza (GLP-1) receptor agonists.

Dr. Vanita Aroda of Brigham and Women’s Hospital presented her case for why metformin should, in fact, remain the first choice for the treatment of type 2 diabetes, in spite of the availability of newer drugs.

“Metformin’s role as initial therapy has been tested in large and long-standing prospective clinical trials, so our evidence basis for initial therapy is actually the strongest,” Aroda said in an interview with dLife.

“We have an average of 17 years of follow up data in the U.K. Prospective Diabetes study, showing the long-term benefits of metformin as initial therapy in patients with type 2 diabetes.”

Aroda, the associate director of diabetes clinical research at Brigham adds, “we don’t have that type of data for any other agent available on the market today.”
When asked why there’s been a push in recent years to change guidelines, she says it’s because there’s been an influx of cardiovascular-outcomes studies that have shown potential benefits of some of the newer drugs.

However, she points out those studies have only been done in those with long-standing diabetes and primarily established cardiovascular disease. “We don’t yet have those studies of these newer drugs in the initial therapy population,” she says.

Dr. Alice Cheng, from the University of Toronto, presented the opposing case and discussed why change is overdue for guidelines and providing data that supports the fact that better options are available.

The theme of her presentation was “five reasons to break up with metformin,” in which she covered all the reasons why metformin is not a good option because it does not treat the core pathophysiologies of type 2 diabetes.

“You do not improve metabolic parameters [with metformin] as well as other drugs,” she states.

She also points out that although metformin lowers HbA1c, it is fairly neutral when it comes to any benefits on weight, blood pressure, and cholesterol.

While cost is another criteria for patients, namely that metformin is affordable, with an average cost of $4.00/month versus the tremendous cost of newer, patent-protected drugs, Dr. Cheng turned the tables:

“Ask yourself which medication would you give your mother and which one would you give your mother-in-law?” she posed at the conference.

“Different doctors have differing viewpoints on their position on whether metformin should be the first line of treatment,” explains Dr. Qin Yang, an endocrinologist and assistant professor of medicine at the University of California, Irvine who attended the debate between Aroda and Cheng. “Some prefer newer drugs, while others prefer older drugs they are comfortable with,” he explains.

Yang says this is an important debate because guidelines that are set in place are very important for clinical practice. “If the ADA abandons metformin as first-line line treatment and opens the guidelines up to newer drugs, then the implications are huge,” he states.

As compelling as Dr. Cheng was in her presentation, Dr. Yang’s viewpoint after the presentation remains unchanged:

“I’m not ready to jump to using newer medications as first-line treatment,” he says, “the clinical trials do show the newer medications are probably more powerful than metformin, however, in a clinical setting we do see metformin is effective, affordable and has a good safety profile.”

In addition, Yang adds metformin may also have potential effects on other diabetes-related conditions such as cancer and dementia, although more clinical studies are needed.

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