SOURCE: Abdul-Ghani M, DeFronzo RA. Diabetes Care 2017;40:1121-1127.

In the absence of contraindications or medication intolerance, metformin has been recommended as the initial treatment choice for patients with type 2 diabetes mellitus (T2DM) for more than a decade. This advice arose from a combination of favorable metformin attributes, including cost, tolerability, safety, and (albeit limited) a relatively favorable cardiovascular profile. But the winds of change are suggesting a potential reconsideration.

Although reduction of microvascular adverse events in T2DM is well-established with “older” antidiabetic agents (e.g., sulfonylureas, metformin, insulin), the authors of this publication argue that our scope of focus for choosing optimum medications should include both efficacy in correcting hyperglycemia as well as the ability of pharmacologic intervention to address the currently recognized basic pathophysiologic defects of T2DM.

Accordingly, glucagon-like peptide-1 (GLP-1) receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide) demonstrate an attractive “better fit.” That is, the four cardinal activities of GLP-1 receptor agonists: glucose-dependent insulin secretion, which minimizes the risk of hypoglycemia; glucose-dependent glucagon inhibition, which blocks excess glucagon while maintaining responsiveness of glucagon to hypoglycemia; improved satiety, potentially empowering more effective adherence to healthful dietary restrictions; and delayed gastric emptying, reducing postprandial glucose excursions. These provide complementary activities that address more of the basic pathophysiologic defects of T2DM than most other agents.

Finally, members of the class of GLP-1 receptor agonists recently have been shown to reduce cardiovascular events. Together, these attributes suggest GLP-1 receptor agonists might be an appropriate initial treatment for T2DM, supplanting metformin.