Semaglutide Improved Beta-Cell Function and Glycemic Control in Type 2 Diabetes

A 12-week regimen of once-weekly semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, benefited beta-cell function and glycemic control in patients with type 2 diabetes, according to data published in Diabetologia.

The researchers of the single-center, double-blind, placebo-controlled, parallel-group trial (ClinicalTrials.gov identifier: NCT02212067) enrolled 75 adult patients with type 2 diabetes. Patients were randomly assigned 1:1 to once-weekly subcutaneous semaglutide 1 mg (0.25, 0.5, 1.0 mg escalated; n=37) or placebo (n=38) for 12 weeks.

 

Eligibility criteria included a hemoglobin A1c level between 6.5% and 9%, a body mass index between 20 kg/m² and 35 kg/m², and treatment with diet and exercise and/or metformin monotherapy with a dose that was unchanged in the 30 days prior to screening.

Co-primary end points were defined as changes from baseline to end of treatment in the first (area under the curve [AUC], 0-10 minutes) and second (AUC, 10-120 minutes) insulin secretion phases, as calculated by the intravenous glucose tolerance test (IVGTT).

Additionally, researchers performed the following tests: an arginine stimulation test (AST), a 24-hour meal stimulation test, and a graded glucose infusion test (GGIT) for determining the insulin secretion rate.

Twelve-week results indicated that after IVGTT, semaglutide significantly increased insulin responses compared with placebo during the first phase (estimated treatment ratio [ETR], 3.02; 95% CI, 2.53-3.60) and second phase (ETR, 2.10; 95% CI, 1.86-2.37; P for both <.0001).

Furthermore, the 24-hour meal test demonstrated decreased fasting, postprandial, and overall (AUC, 0-24 hours) glucose and glucagon responses with semaglutide (P <.0001), while the AST suggested that maximal insulin capacity rose with semaglutide.

In GGIT analysis, semaglutide significantly increased the insulin secretion rate to levels comparable with rates in healthy patients (n=12).

The researchers also documented that semaglutide was well tolerated.

“[T]he results of the current study are consistent with previous findings during treatment with the GLP-1 analogue liraglutide,” the researchers wrote, “and suggest that treatment with semaglutide may offer a protective effect on beta-cell function. In addition, the results show that semaglutide is a promising once-weekly GLP-1 analogue for the treatment of type 2 diabetes, associated with improved beta-cell responsiveness comparable with that observed in healthy individuals.”

The researchers added that the improved glycemic responses observed in the study appeared to be a combined effect on the pancreas of increased insulin secretion and decreased glucagon response

Disclosures: The study was funded by Novo Nordisk A/S. Four researchers report being full-time employees of Novo Nordisk A/S, and one reports financial disclosures with Novo Nordisk and other pharmaceutical manufacturers.

Reference

Kapitza C, Dahl K, Jacobsen JB, Axelsen MB, Flint A. Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial [published online May 19]. Diabetologia. 2017. doi:10.1007/s00125-017-4289-0