Glargine Up-titration vs. Degludec/Liraglutide in Type 2 Diabetes

Study Questions:

Is a fixed ratio of insulin degludec/liraglutide (basal insulin and glucagon-like peptide-1 receptor agonist) noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin?


This was a phase 3, multinational, multicenter, 26-week, randomized, open-label trial of adults with type 2 diabetes with a glycated hemoglobin level of 7-10% (inclusive), who were taking a stable dose of glargine and metformin, and had a body mass index of 40 kg/m2 or lower. Patients were randomized to receive degludec/liraglutide or continued glargine. The primary endpoint was change in glycated hemoglobin from baseline to 26 weeks.


A total of 557 patients were randomized. Glycated hemoglobin reduction was greater with degludec/liraglutide versus glargine (-1.81% for the degludec/liraglutide group vs. -1.13% for the glargine group; estimated treatment difference, -0.59%; 95% confidence interval, -0.74% to -0.45%), meeting criteria for noninferiority (p < 0.001) and statistical superiority (p < 0.001). Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine and fewer confirmed hypoglycemic episodes.


Treatment with degludec/liraglutide compared with up-titration of glargine resulted in greater reduction in glycated hemoglobin after 26 weeks of treatment in patients with uncontrolled type 2 diabetes taking glargine and metformin.


This is a valuable study that draws attention to the merits of a strategy that combines glucagon-like peptide-1 receptor agonist treatment with basal insulin versus up-titration of basal insulin alone. The former may be more efficacious and associated with less weight gain and fewer side effects. Such a strategy should be considered as an alternative to more conventionally up-titrating basal insulin or adding meal-time insulin in patients with uncontrolled type 2 diabetes.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention

Keywords: Diabetes Mellitus, Type 2, Hemoglobin A, Glycosylated, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin, Long-Acting, Metabolic Syndrome X, Metformin, Primary Prevention, Weight Gain, Weight Loss

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