Combination Insulin Degludec/Liraglutide Noninferior to Insulin Glargine in Type 2 Diabetes

Control Blood Glucose
Control Blood Glucose
Type 2 diabetes patients treated with combination insulin therapy had improved glucose control that was on par with up-titration of basal insulin.

For patients with uncontrolled type 2 diabetes who take insulin glargine and metformin, treatment with insulin degludec combined with the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide resulted in noninferior improvement in HbA1c levels when compared with up-titration of insulin glargine, according to data from the DUAL V trial.

Researchers from the University of Texas Southwestern Medical Center conducted a multinational, clinical, phase 3 trial that included 557 participants with uncontrolled type 2 diabetes. Participants were enrolled at 75 treatment centers in 10 different countries from September 2013 to November 2014. They were all taking metformin and basal insulin glargine when they enrolled.

“Many patients who are on an oral agent and basal insulin are unfortunately not at goal glycemia,” said lead author Ildiko Lingvay, MD, MPH, MSCS, associate professor of internal medicine and clinical sciences at University of Texas Southwestern Medical Center, in a press release. “Treatment options for such patients are to either increase the basal insulin dose or to add additional shots of insulin at mealtimes. The downside of both of these approaches is weight gain and hypoglycemia.”

The participants were randomly assigned to continue taking insulin glargine or to switch to daily injections of combination insulin degludec and liraglutide. Participants in the insulin glargine group received sequentially increased insulin doses until their glucose levels were stable. Participants in the insulin degludec/ liraglutide group had their dosage increased based on glucose readings, but there was a maximum dose of degludec 50 U/ liraglutide 1.8 mg.

Ildiko Lingvay, MDIldiko Lingvay, MD
Courtesy of UT Southwestern Medical Center

Baseline HbA1c was 8.4% in the insulin degludec/liraglutide therapy group and 8.2% in the insulin glargine group. HbA1c levels were decreased significantly more in the combination therapy group compared with the insulin glargine group (–1.81% vs –1.13%; estimated treatment difference [ETD]: –0.59%; 95% CI, –0.74 to –0.45) and met the criteria for noninferiority (P<.001) as well as statistical superiority (P<.001).

Participants in the insulin degludec/liraglutide group also lost an average of 1.4 kg, whereas the participants in the insulin glargine group gained an average of 1.8 kg (ETD: –3.20 kg; 95% CI, –3.77 to –2.64; P<.001). Combination therapy was also associated with fewer hypoglycemic episodes than insulin glargine (2.23 vs 5.05 episodes per patient-year exposure; estimated rate ratio: 0.43; 95% CI, 0.30-0.61; P<.001).

The researchcited several limitations to the study, including its open-label design. Additionally, they noted that the findings are only clinically applicable to patients who meet the inclusion and exclusion criteria of the study.

Further assessment of the longer-term safety and efficacy is also needed, the researchers wrote.


  1. Lingvay I, Manghi F, Garcia-Hernandez P, et al; for the DUAL V Investigators. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients with Uncontrolled Type 2 Diabetes: the DUAL V Randomized Clinical Trial. JAMA. 2016;315(9):898-907. doi:10.1001/jama.2016.1252.