Effects of Semaglutide on Beta Cell Function and Glycaemic Control in Participants With Type 2 Diabetes: A Randomised, Double-Blind, Placebo-Controlled Trial

Diabetologia. 2017 Aug;60(8):1390-1399. doi: 10.1007/s00125-017-4289-0. Epub 2017 May 19.

Abstract

Aims/hypothesis: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed.

Methods: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA1c of 6.5-9.0% (47.5-74.9 mmol/mol); BMI 20.0-35.0 kg/m2; and treatment with diet and exercise and/or metformin monotherapy with a dose unchanged in the 30 days prior to screening) were randomised (1:1) to once-weekly s.c. semaglutide 1.0 mg (0.25, 0.5, 1.0 mg escalated) or placebo for 12 weeks. Co-primary endpoints were changes from baseline to end of treatment in the first (AUC0-10 min) and second (AUC10-120 min) insulin secretion phases, as measured by the IVGTT. An arginine stimulation test (AST) and a 24 h meal stimulation test were also conducted. A graded glucose infusion test (GGIT) assessed insulin secretion rate (ISR) in treated participants and a group of untreated healthy participants. Safety endpoints were also assessed.

Results: In total, 37 participants received semaglutide and 38 received placebo. Following IVGTT, for insulin, both AUC0-10min and AUC10-120min were significantly increased with semaglutide (estimated treatment ratio [95% CI] 3.02 [2.53, 3.60] and 2.10 [1.86, 2.37], respectively; p < 0.0001). The 24 h meal test showed reduced fasting, postprandial and overall (AUC0-24h) glucose and glucagon responses with semaglutide (p < 0.0001). The AST showed that maximal insulin capacity increased following semaglutide treatment. During GGIT, semaglutide significantly increased ISR to levels similar to those in healthy participants. Semaglutide was well tolerated.

Conclusions/interpretation: Twelve weeks of once-weekly treatment with semaglutide significantly improved beta cell function and glycaemic control in participants with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT02212067 FUNDING: The study was funded by Novo Nordisk A/S.

Keywords: Beta cell function; Glycaemic control; Placebo-controlled trial; Semaglutide; Type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Metformin / administration & dosage
  • Metformin / therapeutic use
  • Middle Aged
  • Pregnancy
  • Young Adult

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • semaglutide
  • Glucagon-Like Peptides
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT02212067