TY - JOUR

T1 - Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment

T2 - a post-treatment analysis of a randomised placebo-controlled trial

AU - Jensen, Simon Birk Kjær

AU - Blond, Martin Bæk

AU - Sandsdal, Rasmus Michael

AU - Olsen, Lisa Møller

AU - Juhl, Christian Rimer

AU - Lundgren, Julie Rehné

AU - Janus, Charlotte

AU - Stallknecht, Bente Merete

AU - Holst, Jens Juul

AU - Madsbad, Sten

AU - Torekov, Signe Sørensen

N1 - Publisher Copyright: © 2024 The Authors

PY - 2024

Y1 - 2024

N2 - Background: New obesity medications result in large weight losses. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year. Methods: We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Adults with obesity (aged 18–65 years and initial body mass index 32–43 kg/m2) completed an eight-week low-calorie diet-induced weight loss of 13.1 kg (week −8 to 0) and were randomly allocated (1:1:1:1) to one-year weight loss maintenance (week 0–52) with either supervised exercise, the GLP-1 receptor agonist once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo. 166 Participants completed the weight loss maintenance phase. All randomised participants were invited to participate in the post-treatment study with outcome assessments one year after treatment termination, at week 104. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body-fat percentage (week 0–104). The study is registered with EudraCT, 2015-005585-32, and with ClinicalTrials.gov, NCT04122716. Findings: Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. From randomisation to one year after termination of combined exercise and liraglutide treatment (week 0–104), participants had reduced body weight (−5.1 kg [95% CI −10.0; −0.2]; P = 0.040) and body-fat percentage (−2.3%-points [−4.3 to −0.3]; P = 0.026) compared with after termination of liraglutide alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week −8 to 104) compared with participants who had previously received placebo (odds ratio [OR] 7.2 [2.4; 21.3]) and liraglutide (OR 4.2 [1.6; 10.8]). More participants who had previously received supervised exercise maintained a weight loss of at least 10% compared with placebo (OR 3.7 [1.2; 11.1]). During the year after termination of treatment (week 52–104), weight regain was 6.0 kg [2.1; 10.0] larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg [−1.5 to 6.5] compared with after termination of combination treatment. Interpretation: The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. Body weight and body composition were maintained one year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone. Funding: Helsefonden and the Novo Nordisk Foundation.

AB - Background: New obesity medications result in large weight losses. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year. Methods: We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Adults with obesity (aged 18–65 years and initial body mass index 32–43 kg/m2) completed an eight-week low-calorie diet-induced weight loss of 13.1 kg (week −8 to 0) and were randomly allocated (1:1:1:1) to one-year weight loss maintenance (week 0–52) with either supervised exercise, the GLP-1 receptor agonist once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo. 166 Participants completed the weight loss maintenance phase. All randomised participants were invited to participate in the post-treatment study with outcome assessments one year after treatment termination, at week 104. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body-fat percentage (week 0–104). The study is registered with EudraCT, 2015-005585-32, and with ClinicalTrials.gov, NCT04122716. Findings: Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. From randomisation to one year after termination of combined exercise and liraglutide treatment (week 0–104), participants had reduced body weight (−5.1 kg [95% CI −10.0; −0.2]; P = 0.040) and body-fat percentage (−2.3%-points [−4.3 to −0.3]; P = 0.026) compared with after termination of liraglutide alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week −8 to 104) compared with participants who had previously received placebo (odds ratio [OR] 7.2 [2.4; 21.3]) and liraglutide (OR 4.2 [1.6; 10.8]). More participants who had previously received supervised exercise maintained a weight loss of at least 10% compared with placebo (OR 3.7 [1.2; 11.1]). During the year after termination of treatment (week 52–104), weight regain was 6.0 kg [2.1; 10.0] larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg [−1.5 to 6.5] compared with after termination of combination treatment. Interpretation: The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. Body weight and body composition were maintained one year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone. Funding: Helsefonden and the Novo Nordisk Foundation.

KW - Exercise

KW - GLP-1 receptor agonist

KW - Obesity

KW - Physical activity

KW - Weight loss maintenance

U2 - 10.1016/j.eclinm.2024.102475

DO - 10.1016/j.eclinm.2024.102475

M3 - Journal article

AN - SCOPUS:85187561602

VL - 69

JO - EClinicalMedicine

JF - EClinicalMedicine

SN - 2589-5370

M1 - 102475

ER -