From the Guidelines
GLP-2 agonists do not cause significant fat loss or muscle loss as their primary function, instead, they promote intestinal growth and improve nutrient absorption. Unlike GLP-1 agonists, GLP-2 agonists like teduglutide (Gattex) primarily target the gastrointestinal tract to enhance intestinal function and reduce dependence on parenteral nutrition, not for weight management 1. The physiologic effects of GLP-2 appear specific to the gut, with intestinotrophic, anti-secretory, and transit-modulating effects in short bowel patients, and the adverse events, even in supraphysiological doses, seem limited 1. Some key points to consider include:
- GLP-2 receptors are mainly found in the gastrointestinal tract rather than in adipose tissue or muscle
- These medications are typically prescribed for conditions like short bowel syndrome to enhance intestinal function and reduce dependence on parenteral nutrition, not for weight management
- Research suggests GLP-2 may actually have a mild anabolic effect in certain tissues, which could potentially benefit patients with intestinal failure 1
- The effects of GLP-2 on energy absorption seem marginal (less than 250 kcal/day), and the optimal dosage and administration of this new treatment to induce beneficial effects on intestinal secretion, motility, morphology, and absorption in short bowel patients are not known 1
- Teduglutide, a GLP-2 analog, has been able to induce significant intestinal growth in short bowel patients as evaluated by intestinal biopsies, with increases in villus height of 38–45% and crypt depths of 22–18% 1
From the Research
Effects of GLP-2 Agonists on Body Composition
- The effects of GLP-2 agonists on body composition, specifically fat loss or muscle loss, are not directly addressed in the provided studies 2, 3, 4, 5.
- However, a study on GLP-1-based therapies, which are related to GLP-2 agonists, found that weight loss induced by these therapies can result in a reduction of lean mass, but the changes in lean mass may not always reflect changes in muscle mass 6.
- The same study suggests that the reductions in muscle volume with GLP-1RA treatments appear to be adaptive, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality 6.
Resistance Training and Body Composition
- Resistance training has been shown to reduce body fat percentage, body fat mass, and visceral fat in healthy adults 2.
- A review of the evidence on resistance training, visceral obesity, and inflammatory response found that resistance training may promote a negative energy balance and change body fat distribution, potentially leading to better metabolic control 4.
GLP-2 Agonists and Gastrointestinal Function
- A study on the acute effects of a GLP-2 analogue, teduglutide, found that it may have beneficial effects on fluid balance and monosaccharide absorption in adult patients with short bowel syndrome on home parenteral nutrition 5.
- However, this study did not directly address the effects of GLP-2 agonists on fat loss or muscle loss.
GLP-1-Based Therapies and Muscle Mass
- A study on changes in lean body mass with GLP-1-based therapies found that there is heterogeneity in the reported effects of these therapies on lean mass changes in clinical trials 6.
- The study suggests that factors such as population, drug-specific/molecular, and comorbidity effects may contribute to this heterogeneity, and that changes in lean mass may not always reflect changes in muscle mass 6.