Weight loss maintenance with exercise and liraglutide improves glucose tolerance, glucagon response, and beta cell function

Obesity (Silver Spring). 2023 Apr;31(4):977-989. doi: 10.1002/oby.23715.

Abstract

Objective: The aim of this study was to investigate glucose tolerance, glucagon response, and beta cell function during a 1-year maintenance period with either exercise, the glucagon-like peptide-1 receptor agonist liraglutide, or the combination after diet-induced weight loss.

Methods: In this randomized placebo-controlled trial, adults with obesity (BMI: 32-43 kg/m2 ) without diabetes underwent an 8-week low-calorie diet (800 kcal/d) and were randomized to 52 weeks of aerobic exercise, liraglutide 3.0 mg/d, exercise and liraglutide combined, or placebo. Change in glucose and glucagon response to a 3-hour mixed meal test and disposition index, as a measure of beta cell function, were measured.

Results: A total of 195 participants were randomized. After 1 year of treatment, the combination group had decreased postprandial glucose response by -9% (95% CI: -14% to -3%; p = 0.002), improved beta cell function by 49% (95% CI: 16% to 93%; p = 0.002), and decreased glucagon response by -18% (95% CI: -34% to -3%; p = 0.024) compared with placebo. Compared with placebo, liraglutide alone improved postprandial glucose response by -7% (95% CI: -12% to -1%; p = 0.018), but not beta cell function or glucagon. Exercise alone had similar postprandial glucose response, beta cell function, and glucagon response as placebo.

Conclusions: Only the combination of exercise and liraglutide improved glucose tolerance, beta cell function, and glucagon responses after weight loss.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Exercise
  • Glucagon
  • Glucose
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liraglutide* / pharmacology
  • Liraglutide* / therapeutic use
  • Weight Loss

Substances

  • Liraglutide
  • Glucagon
  • Hypoglycemic Agents
  • Glucose
  • Blood Glucose