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

Abstract

AbstractObjectiveThe 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.MethodsIn 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.ResultsA 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.ConclusionsOnly the combination of exercise and liraglutide improved glucose tolerance, beta cell function, and glucagon responses after weight loss.