Scientists at the Comprehensive Center for Weight Management investigated how tirzepatide affects body composition across different age groups, with findings published in the NEJM. The trial enrolled 2,539 adults who were either obese (BMI 30 kg/m² or higher) or overweight (BMI 27 to 30 kg/m²) and who had at least one weight-related complication other than diabetes. Participants were randomly assigned to receive tirzepatide or a placebo via subcutaneous injection at doses of 5 mg, 10 mg, or 15 mg once weekly for 72 weeks.
Body composition was evaluated in 160 participants using dual-energy X-ray absorptiometry, providing data across three age strata: under 50, 50 to 64.9, and 65 and older. Across all age groups, the study found substantial reductions in fat mass, ranging from 33% to 36%, while skeletal muscle mass declined modestly, by 10% to 11%. Overall, weight loss was accompanied by a favorable shift in body composition, with approximately a quarter of total weight loss attributed to muscle loss. Importantly, the magnitude of these changes was remarkably similar across age subgroups, indicating that older individuals did not experience excessive muscle loss compared with younger participants.
Tirzepatide functions as a dual agonist for the GLP-1 and GIP receptors. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are hormones secreted by the gut after meals, triggering insulin release and influencing satiety. By activating both GLP-1 and GIP pathways, tirzepatide enhances blood sugar control and promotes a sense of fullness, which can contribute to greater weight management. This dual receptor activity differentiates tirzepatide from therapies that target a single incretin pathway and may help explain its effects on body composition observed in this study.
The compound is approved in the United States and the European Union for the treatment of type 2 diabetes, but there is currently no approval for obesity management in any country. The new findings add to the ongoing discussion about tirzepatide’s potential role in treating overweight and obesity, alongside lifestyle interventions and other pharmacologic options. As with any medication, considerations such as cardiovascular risk, tolerability, and long-term weight maintenance remain important factors for clinicians and patients when weighing treatment choices. The NEJM report highlights the importance of assessing body composition, not just total weight, to understand the full impact of weight-loss therapies across diverse age groups.