In metformin-treated type 2 diabetes mellitus, weekly dulaglutide was noninferior to daily liraglutide for HbA1c levels

Patients whose diabetes was inadequately controlled on metformin showed similar weight loss, improvement in HbA1c, and adverse events whether they took dulaglutide or liraglutide, a trial found. More than 500 adult Europeans who had an HbA1c of 7% to 10% on 1500 mg/d or more of metformin were randomized to the one of the glucagon-like peptide-1 analogues (dulaglutide, 1.5 mg/wk or liraglutide, titrated up to 1.8 mg/d). At 26 weeks, they had similar reductions in HbA1c (−1.42% vs. −1.36%), although the liraglutide group lost more weight (2.90 kg vs. 3.61 kg). Study authors concluded that weekly dulaglutide was noninferior to daily liraglutide.

The study was published in The Lancet on Oct. 11. The following commentary by Oscar L. Morey-Vargas, MD, and Pankaj Shah, MD, was published in the ACP Journal Club section of the Nov. 18 Annals of Internal Medicine.

Glucagon-like peptide-1 (GLP-1) analogues can be considered as second- or third-line agents for patients with type 2 diabetes that is poorly controlled despite lifestyle modification and metformin therapy. Their modest effects on weight loss and low risk for hypoglycemia may appeal to some patients and their clinicians. Nevertheless, data are lacking on the effects of GLP-1 analogues for important outcomes (e.g., CV events), long-term safety (e.g., risk for pancreatic cancer), and durability of weight loss. These uncertainties, and the high cost of these drugs, have tempered enthusiasm for their use.

Results from AWARD-6 suggest that once-weekly dulaglutide can achieve similar glycemic control and clinically similar but statistically less weight loss compared with daily liraglutide, and that the side effect profile of the 2 GLP-1 analogues is comparable after 6 months of treatment. Both drugs had similar effects on quality of life, although these were not reported in detail. Risk for bias is a concern given the challenge of maintaining allocation concealment with stratified randomization and an average of 10 patients per site, and the lack of blinding in patients and investigators. However, the credibility of the main results is supported by the limited use of alternative antihyperglycemic drugs during the trial, and the weight changes make it implausible that differences in lifestyle favored the dulaglutide group.

What is the clinical relevance of these findings? We still don't know. Further studies are needed to clarify if the ease of administration of once-weekly dulaglutide, which reduces the treatment burden on patients, translates into improved adherence and reduced risk for long-term complications in type 2 diabetes.