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

Importance Achieving glycemic control remains a challenge for patients with type 2 diabetes, even with insulin therapy. Objective To assess whether a fixed ratio of insulin degludec/liraglutide was noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin. Design, Setting, and Participants Phase 3, multinational, multicenter, 26-week, randomized, open-label, 2-group, treat-to-target trial conducted at 75 centers in 10 countries from September 2013 to November 2014 among 557 patients with uncontrolled diabetes treated with glargine (20-50 U) and metformin (≥1500 mg/d) with glycated hemoglobin (HbA 1c ) levels of 7% to 10% and a body mass index of 40 or lower. Interventions 1:1 randomization to degludec/liraglutide (n = 278; maximum dose, 50 U of degludec/1.8 mg of liraglutide) or glargine (n = 279; no maximum dose), with twice-weekly titration to a glucose target of 72 to 90 mg/dL. Main Outcomes and Measures Primary outcome measure was change in HbA 1c level after 26 weeks, with a noninferiority margin of 0.3% (upper bound of 95% CI, 1c level, change in body weight, and rate of confirmed hypoglycemic episodes. Results Among 557 randomized patients (mean: age, 58.8 years; women, 49.7%), 92.5% of patients completed the trial and provided data at 26 weeks. Baseline HbA 1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA 1c level reduction was greater with degludec/liraglutide vs glargine (−1.81% for the degludec/liraglutide group vs −1.13% for the glargine group; estimated treatment difference [ETD], –0.59% [95% CI, –0.74% to –0.45%]), meeting criteria for noninferiority ( P P , P , P Conclusions and Relevance Among patients with uncontrolled type 2 diabetes taking glargine and metformin, treatment with degludec/liraglutide compared with up-titration of glargine resulted in noninferior HbA 1c levels, with secondary analyses indicating greater HbA 1c level reduction after 26 weeks of treatment. Further studies are needed to assess longer-term efficacy and safety. Trial Registration clinicaltrials.gov Identifier:NCT01952145