Exercise, GLP-1 receptor agonist, or combined approach explored in year-long study

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Feb 29 2024

A recent eClinicalMedicine study compares the extent of maintenance of weight loss after one-year termination of active intervention with glucagon-like peptide-1 (GLP-1) receptor agonist, a supervised exercise program, or a combination of both.

Study: 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. Image Credit: photobyphotoboy / Shutterstock.com

Background

Obesity is a health condition associated with the accumulation of excess body fat. Several studies have indicated that obesity influences the incidence of numerous health conditions including type 2 diabetes and cardiovascular events.

In recent years, many treatments and weight loss programs have been developed to reduce obesity. For example, GLP-1 receptor agonists have received approval from global regulatory bodies for the treatment of obesity and type 2 diabetes.

GLP-1 receptor agonists have been shown to reduce appetite, which leads to a less food intake. As compared to single weight loss treatment, combinational treatment with the GLP-1 receptor agonist liraglutide and a supervised exercise program exhibited greater weight loss maintenance and improved body composition.

GLP-1 receptor agonists like semaglutide and tirzepatide have caused a greater weight loss as compared to a placebo-treated control group after 68 and 78 weeks of treatment, respectively. Although multiple studies have reported the positive effects of these obesity interventions, long-term adherence to these treatments is difficult due to their adverse gastrointestinal effects and high cost.

Most obesity interventions are discontinued after one year. Furthermore, many studies have shown that discontinuation of GLP-1 receptor agonists leads to weight gain.

These observations emphasize the importance for continued usage of GLP-1 receptor agonists as medication for prolonged favorable effects. Nevertheless, a new strategy is needed to minimize weight gain, even after termination of weight loss medication.

Exercise is a low-cost intervention that can be continued for prolonged periods and is an extremely effective weight loss intervention. Thus, it is important to evaluate whether a combination of exercise and GLP-1 receptor agonist treatment improves weight loss maintenance after termination of the treatment.

About the study

The current randomized and controlled trial hypothesized that weight loss and body composition could be better maintained after one year of termination of active treatment with a supervised exercise program and GLP-1 receptor agonist or a combination of both for one year. Moreover, a combinational intervention was hypothesized to present a better effect as compared to a single GLP-1 receptor agonist treatment.

Obese individuals between 18 and 65 years of age were recruited in the study. Participants with a history of chronic diseases including diabetes were excluded from the study cohort.

All study participants were subjected to an eight-week low-calorie diet and were randomly assigned to four groups including liraglutide and usual physical activity, placebo and usual physical activity, combined exercise and placebo, combined exercise plus liraglutide, as well as liraglutide and usual physical activity for 52 weeks.

One year after completion of 52 weeks of the aforementioned interventions, the participants were invited to a post-treatment study, in which weight maintenance of the participants was assessed.

Study findings

A total of 109 individuals participated in the post-treatment study that was conducted between December 17, 2018, to Decembers 17, 2020. Importantly, the characteristics of the participants in all intervention groups were similar.

Participants who were assigned to combinational treatment of supervised exercise and GLP-1 receptor agonist treatment exhibited greater weight loss maintenance and reduction in body fat after one year of treatment. Interestingly, individuals who received liraglutide alone exhibited the maximum weight gain of six kg after one year of intervention termination. 

Despite the weight loss that occurred in the initial phase of intervention, a disproportional amount of weight gain occurred in participants who received supervised exercise alone and liraglutide alone after one year of treatment termination. More weight gain after one year of intervention termination was observed in the liraglutide groups group.

The liraglutide alone group exhibited better benefits on body composition, healthy body weight, and glucose levels. However, the combination of liraglutide with exercise led to an effective lowering of fat percentage, waist circumference, and fat mass.

Conclusions

The current study has some limitations including the small number of participants in the placebo group, particularly in the post-treatment study. In all treatment groups, participants who attended the post-treatment study were those who experienced positive effects during active interventions.

Despite these limitations, the study findings suggest that adding supervised exercise with pharmacotherapy enables better maintenance of healthy body weight and body composition one year after treatment termination.