Resistance exercise attenuates lean mass loss during tirzepatide therapy

A 40-week randomized trial tested whether resistance exercise could protect lean tissue in adults with overweight or obesity taking tirzepatide. The 120 participants, including 60 men and 60 postmenopausal women, received weekly tirzepatide and were assigned either to usual activities or to three supervised resistance-training sessions each week. Exercise adherence was high at 91%, and most participants tolerated dose escalation to 15 mg. Both groups lost about 22 kg, with no meaningful difference in total fat loss: resistance training did not reduce the medication’s overall weight-loss effect.

The main benefit was preservation of lean soft tissue. Participants taking tirzepatide alone lost an average of 4.67 kg of lean mass, compared with 3.57 kg among those who also exercised - about 1.1 kg less loss with resistance training. Muscle strength changed during treatment, while improvements in blood pressure, blood sugar, insulin and blood lipids were broadly similar between groups, suggesting exercise did not diminish tirzepatide’s cardiometabolic benefits. Side effects, chiefly gastrointestinal symptoms such as nausea, vomiting, constipation and diarrhea, occurred at similar rates in both groups; six serious events were judged unrelated to treatment or exercise. The results indicate that regular resistance training can partly offset lean-mass loss during substantial medication-assisted weight reduction, though it does not prevent that loss entirely.