John B. Buse, MD, PhD

Disclosures

November 10, 2014

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Conrad Eng and coworkers[1] from Canada did a beautiful job in a systematic review and meta-analysis of the trials combining GLP-1 receptor agonists with basal insulin. They showed that, in comparison with basal insulin alone, this combination was associated with about a 0.4% greater reduction in hemoglobin A1c. The combination also was associated with a lower risk for hypoglycemia, and with weight loss as opposed to weight gain.

They also looked at studies that randomly assigned patients to either the combination of GLP-1 with basal insulin, or the combination of basal insulin with rapid-acting insulin, or the multiple daily injection format. In that comparison, they showed that the combination of GLP-1 receptor agonist plus basal insulin led to a marginally better improvement in hemoglobin A1c, but it also led to much lower rates of hypoglycemia—30% to 40% lower—and an even bigger difference in weight loss.

I think this systematic review and meta-analysis really cements the role of GLP-1 receptor agonists and basal insulin as a "go-to" combination in the management of type 2 diabetes because it harnesses the power of these two exceptional glucose-lowering agents, and it does so by mitigating the risk for side effects of each.

In a related commentary,[2] I pointed out that the DUAL-II study (published recently in Diabetes Care[3]) was a randomized, blinded study comparing the preformulated combination of liraglutide and insulin degludec vs degludec (a basal insulin) alone. The rates of nausea were essentially identical between basal insulin alone and this combination product. Minimizing the total exposure and slowing the rate of administration seem to also minimize the nausea associated with GLP-1 receptor agonists.

I think this is a very exciting combination. Congratulations to Conrad Eng and his colleagues for the wonderful publication in The Lancet.

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