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Healthy Weight-Loss Maintenance With Exercise, GLP-1 Receptor Agonist, or Both Combined Followed by 1 Year Without Treatment
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This post-treatment study, an extension of a randomised controlled trial, investigated whether weight loss and improved body composition are sustained at 1 year after termination of active treatment with a GLP-1 receptor agonist, a supervised exercise program, or both combined. Participants had decreased body weight and body fat percentage from randomisation to 1 year after termination of the combination treatment compared with after termination of liraglutide alone. More participants maintained weight loss of at least 10% of initial body weight at 1 year after termination of the combination treatment compared with placebo alone. The weight regain was larger after termination of liraglutide compared with after termination of the combination treatment.
- Supervised exercise together with obesity medications improved weight maintenance after treatment termination compared with treatment with obesity medications alone. Body weight and body composition were maintained 1 year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBackground
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.
Additional Info
Disclosure statements are available on the authors' profiles:
This was a randomized control trial of 195 adults (aged 18–65 years) with obesity (BMI, 32–43 kg/m2) in Copenhagen, Denmark, who were recruited between August 29, 2016, and September 14, 2018. All participants completed an 8-week low-calorie diet during a run period and then were randomly allocated to 1-year weight loss maintenance (week 0–52) with either supervised exercise, the GLP-1 receptor agonist (GLP-1 RA) once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo in a 1:1:1:1 fashion. Between December 17, 2018, and December 17, 2020, 109 participants attended the post-treatment study, which evaluated weigh loss maintenance at 1 year after therapy. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to 1 year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body fat percentage (week 0–104). Among the patients who attended the post-treatment follow-up, 40% were male, average age was 44.1 ± 12.2 years, and BMI was 32.7 ± 3 kg per m2. Patients on average did not have evidence of hypertension, hyperlipidemia, or diabetes. Patients assigned to supervised exercise and liraglutide 3.0 mg had the highest overall weight-loss maintenance (63% ≥5% weight loss), followed by supervised exercise (58% ≥5% weight loss), followed by placebo (45% ≥5% weight loss), followed by liraglutide (33% ≥5% weight loss). Although an interesting trend, the only finding that was statistically significant was the comparison of the liraglutide group with the liraglutide and exercise group (estimated mean difference, −5.1 kg; 95% CI, −10 to −0.2; P = .040) The largest changes in fat mass, and waist circumference occurred with a combination of liraglutide and exercise again, only showing statistical significance with the liraglutide group (estimated mean difference, −2.3% kg; 95% CI, −4.3 to −0.2; P = .040). GLP-1 RA therapy resulted in the greatest initial weight loss; however, liraglutide alone also resulted in the greatest weight regain when medical therapy was stopped. Exercise did not cause the most substantial weight loss, but was the most important factor in weight maintenance after discontinuation of all interventions. This is consistent with known data on weight maintenance and exercise. In other studies, mild weight loss (2%–3%) occurs at 150 minutes of exercise per week, with more substantial weight loss at 300 minutes or more per week. Importantly, exercise improves outcomes for complications of obesity, such as diabetes, coronary disease, metabolic-associated liver disease, and hypertension, by improving insulin sensitivity, muscle mass, and cardiovascular health beyond the effects of weight loss alone.1-5 In addition, exercise helps prevent muscles loss that occurs with weight loss.6 A concern about this study is that weight loss agents are meant to be taken continuously for the chronic disease of obesity. The generalizability of these data may be limited, as the Copenhagen is demographically >90% White.7 These findings are nonetheless useful to confirm prior findings on weight maintenance and give an important perspective on outcomes in patients that may not be able to tolerate long-term GLP-1 RA therapy. Finally, they confirm that effective weight-loss management requires a comprehensive plan in which exercise is an integral piece.
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