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In recent years, the quest for effective weight loss strategies has led to the exploration of various interventions, including pharmacological treatments and lifestyle modifications. One such pharmacological treatment is liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), which has shown promise in managing obesity. When combined with exercise, the potential benefits on weight loss and bone health become even more intriguing. This article delves into a study that investigates the effects of exercise, liraglutide, and their combination on weight loss and bone mineral density (BMD) in individuals with obesity.

Study Design and Participants

The study in question was a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. The participants included adults aged 18 to 65 years with a body mass index (BMI) ranging from 32 to 43, indicating obesity. Importantly, individuals with diabetes were excluded from the study to focus on the effects of the interventions on non-diabetic obese individuals.

Participants underwent an initial 8-week low-calorie diet, consuming approximately 800 kcal per day. Those who achieved at least a 5% reduction in their initial body weight were then randomly assigned to one of four groups for a 52-week intervention phase: exercise alone, liraglutide alone, a combination of exercise and liraglutide, or a placebo.

Interventions and Compliance

The exercise intervention began with a 6-week ramp-up phase, followed by a regimen where participants were encouraged to attend group exercise sessions twice a week and perform individual exercises twice a week. Group sessions included 30 minutes of indoor cycling and 15 minutes of circuit training, both of which were designed to be of vigorous intensity. Individual exercises varied but were recommended to be of moderate-to-vigorous intensity, with popular choices being cycling, running, brisk walking, and individual circuit training. Heart rate monitors were used to ensure adherence to the exercise intensity guidelines.

Liraglutide or a volume-matched placebo was administered as a once-daily subcutaneous injection. The study reported high compliance rates, with the mean exercise volume being 118 minutes per week at an intensity of 78% of maximum heart rate in the exercise group and 111 minutes per week at 79% of maximum heart rate in the combination group.

Weight Loss Outcomes

The study's findings on weight loss were significant. The total estimated mean change in weight loss during the study was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and an impressive 16.88 kg in the combination group. These results highlight the superior efficacy of the combination of exercise and liraglutide in achieving weight loss compared to either intervention alone or the placebo.

Changes are shown for body weight (A), body fat percentage (B), fat mass (C), and lean mass (D). Values are estimated mean changes in kilograms after a low-calorie diet (weeks −8 to 0) and 52 weeks after randomization to treatment with placebo, exercise, liraglutide, or the combination of exercise and liraglutide. The shaded area indicates the period of the low-calorie diet. Results are from the intention-to-treat population (all randomized participants). Randomization was done at week 0, immediately after the low-calorie diet. Error bars are standard errors of the mean.

Bone Health Outcomes

A major concern with weight loss is the potential for concomitant bone loss, which can increase the risk of fractures. The study investigated changes in BMD at clinically relevant sites, including the hip, lumbar spine, and distal forearm. The results revealed that the combination of exercise and liraglutide not only led to the most significant weight loss but also preserved BMD at these critical sites. In contrast, liraglutide alone was associated with a reduction in hip and spine BMD compared to placebo or exercise alone.

The preservation of BMD in the combination group is particularly noteworthy given the substantial weight loss achieved. This finding suggests that the mechanical strain of exercise may play a crucial role in maintaining bone health during weight loss. Exercise has been shown to increase bone formation and preserve bone health, which is essential for reducing the risk of fractures, especially at sites like the hip and spine that are associated with higher mortality risk when fractured.

Implications and Future Directions

The study's findings have several important implications for obesity management and bone health. Firstly, the combination of exercise and liraglutide emerges as a highly effective weight loss strategy that also preserves bone health. This dual benefit is crucial for individuals with obesity, as it addresses both weight management and the prevention of bone-related complications.

Secondly, the study underscores the importance of incorporating exercise into weight loss programs, particularly when using pharmacological treatments like GLP-1 RAs. Exercise not only enhances weight loss outcomes but also mitigates the adverse effects on bone health that can accompany significant weight reduction.

Future research should continue to explore the mechanisms underlying the preservation of BMD with combined exercise and pharmacological treatments. Additionally, investigating other inflammatory markers and their roles in weight loss and bone health could provide further insights into optimizing obesity management strategies.

Conclusion

In conclusion, the combination of exercise and liraglutide represents a promising approach to achieving substantial weight loss while preserving bone health in individuals with obesity. This study highlights the synergistic effects of these interventions and emphasizes the importance of a comprehensive approach to obesity management that includes both lifestyle modifications and pharmacological treatments. As the prevalence of obesity continues to rise, such integrated strategies will be essential in addressing the multifaceted challenges associated with this condition.

Read Paper│JAMA Network