TY - JOUR

T1 - Weight loss maintenance with exercise and liraglutide improves glucose tolerance, glucagon response, and beta cell function

AU - Jensen, Simon B K

AU - Juhl, Christian R.

AU - Janus, Charlotte

AU - Lundgren, Julie R

AU - Martinussen, Christoffer

AU - Wiingaard, Christoffer

AU - Knudsen, Cecilie

AU - Frikke-Schmidt, Ruth

AU - Stallknecht, Bente M

AU - Holst, Jens J.

AU - Madsbad, Sten

AU - Torekov, Signe S.

N1 - © 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.

PY - 2023

Y1 - 2023

N2 - 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/m 2 ) 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.

AB - 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/m 2 ) 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.

KW - Adult

KW - Humans

KW - Liraglutide/pharmacology

KW - Glucagon

KW - Hypoglycemic Agents/therapeutic use

KW - Weight Loss

KW - Exercise

KW - Glucose

KW - Double-Blind Method

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2/drug therapy

U2 - 10.1002/oby.23715

DO - 10.1002/oby.23715

M3 - Journal article

C2 - 36942420

VL - 31

SP - 977

EP - 989

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 4

ER -