Dataset Information

Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial.

ABSTRACT:

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.

SUBMITTER: Jensen SBK

PROVIDER: S-EPMC10965408 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial.

Jensen Simon Birk Kjær SBK Blond Martin Bæk MB Sandsdal Rasmus Michael RM Olsen Lisa Møller LM Juhl Christian Rimer CR Lundgren Julie Rehné JR Janus Charlotte C Stallknecht Bente Merete BM Holst Jens Juul JJ Madsbad Sten S Torekov Signe Sørensen SS

EClinicalMedicine 20240219

<h4>Background</h4>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.< ...[more]

PMID: 38544798

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Project description:BackgroundRecent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain.MethodsIn a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance.ResultsSoluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml(-1) (-3.0 (95% confidence interval (CI)=-0.5 to -5.5)), P<0.001 and free leptin index decrease was 43% smaller; -62±15 vs -109±20 (-47 (95% CI=-11 to -83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (-2.3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P<0.001. Fasting glucose was decreased by an additional -0.2±0.1 mmol l(-1) in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), P<0.005. Meal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05.ConclusionsThe weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3-36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Project description:ImportanceA major concern with weight loss is concomitant bone loss. Exercise and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent weight loss strategies that may protect bone mass despite weight loss.ObjectiveTo investigate bone health at clinically relevant sites (hip, spine, and forearm) after diet-induced weight loss followed by a 1-year intervention with exercise, liraglutide, or both combined.Design, setting, and participantsThis study was a predefined secondary analysis of a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. Eligible participants included adults aged 18 to 65 years with obesity (body mass index of 32-43) and without diabetes. Data analysis was conducted from March to April 2023, with additional analysis in February 2024 during revision.InterventionsAfter an 8-week low-calorie diet (800 kcal/day), participants were randomized to 1 of 4 groups for 52 weeks: a moderate- to vigorous-intensity exercise program (exercise alone), 3.0 mg daily of the GLP-1 RA liraglutide (liraglutide alone), the combination, or placebo.Main outcomes and measuresThe primary outcome was change in site-specific bone mineral density (BMD) at the hip, lumbar spine, and distal forearm from before the low-calorie diet to the end of treatment, measured by dual-energy x-ray absorptiometry in the intention-to-treat population.ResultsIn total, 195 participants (mean [SD] age, 42.84 [11.87] years; 124 female [64%] and 71 male [36%]; mean [SD] BMI, 37.00 [2.92]) were randomized, with 48 participants in the exercise group, 49 participants in the liraglutide group, 49 participants in the combination group, and 49 participants in the placebo group. The total estimated mean change in weight losses during the study was 7.03 kg (95% CI, 4.25-9.80 kg) in the placebo group, 11.19 kg (95% CI, 8.40-13.99 kg) in the exercise group, 13.74 kg (95% CI, 11.04-16.44 kg) in the liraglutide group, and 16.88 kg (95% CI, 14.23-19.54 kg) in the combination group. In the combination group, BMD was unchanged compared with the placebo group at the hip (mean change, -0.006 g/cm2; 95% CI, -0.017 to 0.004 g/cm2; P = .24) and lumbar spine (-0.010 g/cm2; 95% CI, -0.025 to 0.005 g/cm2; P = .20). Compared with the exercise group, BMD decreased for the liraglutide group at the hip (mean change, -0.013 g/cm2; 95% CI, -0.024 to -0.001 g/cm2; P = .03) and spine (mean change, -0.016 g/cm2; 95% CI, -0.032 to -0.001 g/cm2; P = .04).Conclusions and relevanceIn this randomized clinical trial, the combination of exercise and GLP-1RA (liraglutide) was the most effective weight loss strategy while preserving bone health. Liraglutide treatment alone reduced BMD at clinically relevant sites more than exercise alone despite similar weight loss.Trial registrationEudraCT: 2015-005585-32.

Project description:BackgroundIdentifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss.MethodsThis was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model.ResultsThe diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (- 0.37, 95% CI - 0.58 to - 0.16, P < 0.001) and the combination treatment (- 0.48, 95% CI - 0.70 to - 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03).ConclusionThe combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments. Trial registration EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716.

Dataset Information

Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial.

Background

Methods

Findings

Interpretation

Funding

Publications

Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial.

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