Current thinking suggests that combining GLP-1 medication with exercise may be more effective for weight loss than relying on either approach alone. But is this truly the case?

 

Given that some patients may face challenges in tolerating, affording, or accessing GLP-1 medications, it’s crucial to explore alternative options for weight loss and management. Exercise is one such alternative. While there may be associated costs (e.g., gym memberships, fitness classes, or purchasing equipment like a smartwatch or heart rate monitor), exercise remains a cost-effective strategy for weight loss. However, the question remains: Can exercise alone sustain long-term weight loss?

One clinical challenge is the potential for weight regain after disconuing a GLP-1 medication. Current thinking suggests that combining GLP-1 medication with exercise may be more effective for weight loss than relying on either approach alone. But is this truly the case?

 

A recent study, partially funded by Novo Nordisk, examined the sustainability of weight loss after stopping GLP-1 medication. The findings suggest that combining GLP-1 therapy with supervised exercise could help prevent weight regain following the discontinuation of GLP-1 use.

A 2024 Study on Weight Regain: Comparing GLP-1 Therapy, Exercise, and Their Combination

A 2024 study¹ expanded on previous research from a randomized controlled trial investigating weight regain following the discontinuation of a placebo.² Adults with serious chronic conditions, including diabetes, were excluded from participation.³ Prior to randomization, participants (n = 109) completed an eight-week low calorie diet of 800 kcal/day. Only those who achieved a five percent weight loss were eligible for inclusion, provided they met the exclusion criteria. After this eight-week period, participants were randomly assigned in a 1:1:1:1 ratio into four groups: (1) Usual activity + placebo, (2) Exercise + placebo, (3) Usual activity + GLP-1 therapy, and (4) Exercise + GLP-1 therapy. Liraglutide was the GLP-1 therapy used in the study.

The GLP-1 therapy and placebo were volume-matched, starting at 0.6 mg daily, with weekly escalations of 0.6 mg until the maximum tolerated dose, up to a limit of 3.0 mg. After 52 weeks, both treatments were discontinued.

 

Exercise began with a six-week introductory phase, gradually increasing in intensity. From week seven onward, participants attended twice-weekly group sessions that included moderate to vigorous indoor cycling followed by circuit training. Exercise was monitored with sports watches and heart rate monitors. At the end of the 52 weeks, the supervised exercise program concluded, and participants returned their sports watches and heart monitors.

 

During the post-treatment phase, there was no contact between participants and study personnel until the one-year follow-up. Primary outcomes included changes in body weight, body fat percentage, metabolic health, lean mass, waist and hip circumference, HbA1c, and blood pressure, among others.

 

Results:

 

1. GLP-1 alone: Participants in the liraglutide-only group regained 9.6 kg during the year following treatment, representing an 8.7 kg net gain compared to the end of the initial diet phase. The study authors reported that nearly two-thirds of the weight lost was regained, supporting previous research on semaglutide discontinuation.⁴ Notably, glycemic control also declined during the post-treatment year.

 

2. Exercise alone: Participants in the exercise-only group regained 3.6 kg but maintained greater reductions in fat mass and fat percentage. The authors suggest that these results may be attributed to behavioral adaptation.

 

3. GLP-1 + Exercise: The combined group demonstrated the most success, regaining only 7.1 kg during the post-treatment year, compared to 9.6 kg in the GLP-1-only group. By week 104, participants in this group remained below their baseline weight. Furthermore, a higher proportion of participants in the combined group maintained ≥ 10 percent weight loss from baseline, suggesting that supervised exercise can enhance the weight loss achieved through GLP-1 therapy.

As noted above, participants in the exercise only condition may have benefitted from behavioral adaptation or new habit formation. Habit formation, as documented in previous research, has been shown to a successful weight loss strategy.⁵ Because exercise positively affects metabolic rate and cardiometabolic characteristics, it is not surprising that when paired with a GLP-1 medication these benefits are amplified.

Implications for Clinical Practice

While GLP-1 medications can help patients achieve clinically significant weight loss, the effects are often diminished once treatment is discontinued. As a result, health care providers play a crucial role in managing patient expectations about the potential for weight regain after stopping GLP-1 therapy. While exercise alone can lead to weight loss and maintenance, it generally results in smaller weight reductions compared to GLP-1 treatment. However, evidence suggests that combining GLP-1 therapy with supervised exercise can contribute to more sustainable weight loss post-treatment.

In addition to exercise, health care providers should consider recommending supervised weight management programs that incorporate meal replacements and behavioral education. These programs can support long-term weight management by addressing the behavioral and nutritional aspects of weight loss. Meal replacements offer a structured approach to reducing calorie intake, while behavioral education helps patients develop healthy habits for maintaining weight loss.

 

Health care providers should engage patients in conversations about the benefits of exercise during GLP-1 treatment, as well as the likelihood of weight regain once treatment ends. It’s important to collaborate with patients to identify appropriate, structured exercise programs and discuss the potential benefits of using activity trackers or heart-rate monitors as part of a post-GLP-1 exercise regimen. By taking a comprehensive, patient-centered approach, health care providers can optimize long-term weight management outcomes, even after discontinuation of GLP-1 therapy.

Source(s):

1 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 randomized placebo-controlled trial

2 Healthy weight loss maintenance with exercise: Liraglutide or both combined

3 Protocol for randomized controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very-low calorie diet

4 Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP-1 trial extension

5 Habit-based interventions for weight loss maintenance in adults with overweight and obesity: A randomized control trial

 

About the Author: Dr. Dawn M. Sweet has over 20 years of experience in the field of communication. Dr. Sweet has given several invited talks to and workshops for academic and private sector audiences on the role of nonverbal and verbal communication in achieving positive outcomes and mitigating bias. Her research has been published in several top ranked peer-review journals, and it has been featured on NPR’s River to River / All Things Considered, Buzzfeed, and Science Daily. Her research has also been used to inform expert testimony.

About Robard: Robard Corporation has proudly set the standard for medical weight management since 1976. Our evidence-based weight management programs and science-driven nutritional products are the cornerstone of success for leading hospitals, physicians, and weight management clinics across the United States. To learn more about us and how we can help your practice and patients, visit us online www.Robard.com, email us at info@robard.com, or call (800) 222-9201.