Notes on Ozempic and other weight loss GLP-1 medications; "Skinny fat"

What happens when you stop taking medications like Ozempic (semaglutide), Monjauro (tirzepatide) and others of the same class?

GLP-1 receptor agonists are a class of medications initially developed for treating type 2 diabetes. However, they have gained attention for their significant weight loss effects.  This study investigated long-term weight loss sustainability after terminating treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist (liraglutide), supervised exercise, or a combination of both. After an initial weight loss phase (13.1 kg over eight weeks), 166 participants (aged 18-65, BMI 32-43 kg/m²) were randomized into four groups: supervised exercise, liraglutide, both, or placebo for one year. Notably, weight regain was significantly higher after stopping liraglutide alone compared to stopping supervised exercise or the combination treatment. The findings suggest that combining supervised exercise with obesity medication can enhance long-term weight maintenance post-treatment termination.

Ozempic and medications of the same class result in loss of lean mass as well as fat that can result in increased frailty in the elderly.

This narrative review discusses the impact of new anti-obesity medications, particularly those targeting gut-derived hormones (incretins), on lean mass loss and the role of resistance exercise in preserving muscle. Medications like glucagon-like peptide 1 receptor agonists (GLP-1RAs) and dual or triple agonists (like tirzepatide and retatrutide) can lead to significant weight loss (15-24%) in individuals with obesity, along with improvements in metabolic health markers. However, these medications also result in a rapid loss of lean mass (about 10% or roughly 6 kg), akin to aging by a decade.

Maintaining muscle mass is essential to prevent sarcopenia and frailty, conditions associated with increased morbidity and mortality. Research shows that supervised resistance training for over 10 weeks can significantly increase lean mass (approximately 3 kg) and strength (around 25%). Additionally, combining aerobic exercise with liraglutide after a low-calorie diet helps maintain weight loss better than either intervention alone.

The review advocates for incorporating tailored resistance exercise training as a complementary approach to incretin therapy, aiming to optimize body composition by preserving lean mass while promoting fat loss.