Type 2 Diabetes Debate: Metformin Versus GLP-1 Receptor Agonists

The August 2017 issue of Diabetes Care contains 2 opinion pieces of great interest to pharmacists. Both address a key question—is it time to change the type 2 diabetes treatment paradigm? One piece written by Silvio E. Inzucchi, MD from the Yale School of Medicine in New Haven, Connecticut provides evidence in favor of keeping the existing paradigm (using metformin as the cornerstone of treatment).

Dr. Inzucchi reviews evidence that metformin has few associated adverse events, little effect on weight, low risk of hypoglycemia, and cardiovascular benefits. In addition, metformin is a reasonably-priced drug that is effective in most patients. It's important to note that every newly developed drug is tested against metformin because it is so widely used and so effective. However, despite decades of metformin use, clinical researchers still don't know how it works.

The author acknowledged that some of the newer glucose-lowering drugs are equally or more effective than metformin in some patients, and have now been proven to have long-term benefits. He reported that the only drug that might be preferred over metformin as initial monotherapy for type 2 diabetes would be a drug that is more potent, provides a longer duration of effectiveness, or improves long-term microvascular or macrovascular complications significantly. To date, evidence proving this definitively for other agents is lacking in his opinion.

In a counterpoint article, Muhammad Abdul-Ghani, MD, PhD, and Ralph A. Defronzo, MD, from Hamar General Hospital in Qatar and the University of Texas Health Science Center in San Antonio, Texas, respectively, answer the same question. The cornerstone of their argument is that current type 2 diabetes management still relies on lowering plasma glucose concentrations rather than correcting underlying metabolic abnormalities.

Using their understanding of clinical research, the authors recommended that the GLP-1 receptor agonists should be first-line therapy in type 2 diabetes. They invoke the Ominous Octet theory, noting that the GLP-1 receptor antagonists correct 6 factors in the Octet and that metformin is not an insulin sensitizer in muscle or adipocytes. Additionally, the authors indicated that GLP-one receptor agonists have a good safety profile, and in terms of gastrointestinal adverse events, their effects are similar to that of metformin.

Perhaps their strongest point is that 2 large studies have definitively shown that the GLP-1 receptor agonists confer cardiovascular benefit.

Both authors emphasized that overall, treatment options for type 2 diabetes have expanded and pharmacists are in the advantageous state of having a choice when presented with patients whose diabetes is newly diagnosed or uncontrolled. Above all, review of these 2 articles reminds pharmacists that health care has its basis in science, but its successful execution is an art.

Reference

Inzucchi SE. Is It Time to Change the Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain the Foundation Therapy for Type 2 Diabetes. Diabetes Care. 2017;40(8):1128-1132.

Abdul-Ghani M, DeFronzo RA. Is It Time to Change the Type 2 Diabetes Treatment Paradigm? Yes! GLP-1 RAs Should Replace Metformin in the Type 2 Diabetes Algorithm. Diabetes Care. 2017;40(8):1121-1127.