Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

Apr 30, 2024Diabetes care

Can Resistance Exercise Improve Body Composition Changes from Incretin-Based Weight Loss Drugs?

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Abstract

Incretin-based antiobesity medications may cause ∼10% loss of lean mass in adults with overweight and obesity.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) can induce ∼15-24% weight loss.
Combining GLP-1RA with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists may enhance weight loss effects.
Significant loss of lean mass from these medications is comparable to aging by a decade or more.
Supervised resistance exercise training lasting over 10 weeks can lead to increases of ∼3 kg in lean mass and ∼25% in strength.
Combining aerobic exercise with liraglutide after a low-calorie diet improves weight loss maintenance compared to either intervention alone.
Recommending resistance exercise alongside incretin therapy may help preserve lean mass while facilitating fat loss.

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This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.

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Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

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