Summary
In a 40-week randomized trial of 120 adults with overweight or obesity, adding supervised resistance exercise to tirzepatide reduced loss of DXA-measured lean soft tissue and increased tested muscle strength. Weight and fat loss were similar between groups.
A randomized trial published in Nature Medicine found that adding supervised resistance exercise to tirzepatide treatment reduced the loss of lean soft tissue and improved measured muscle strength over 40 weeks. Weight and fat loss were similar whether participants exercised or not.
Contents
Trial design and results
The trial assigned 120 adults with overweight or obesity to weekly tirzepatide injections, either with usual activities or alongside resistance training. Participants in the exercise group attended three supervised, one-hour sessions each week. The intervention lasted 40 weeks, and researchers measured body composition and strength at eight-week intervals.
At week 40, participants receiving tirzepatide alone had lost an average of 22.61 kg, compared with 22.28 kg in the exercise group. Fat-mass loss was also similar: 17.19 kg and 17.98 kg, respectively. The main difference was in total lean soft tissue: the tirzepatide-only group lost 4.67 kg, while the group that also trained lost 3.57 kg. The adjusted difference between groups was 1.09 kg (97.5% confidence interval, 0.43–1.75).
Lean tissue and muscle strength
Lean soft tissue is a body-composition measure that includes skeletal muscle but is not identical to muscle mass. The researchers measured it using dual-energy X-ray absorptiometry (DXA), which estimates fat mass, lean soft tissue and bone mineral content. Resistance training also reduced the loss of appendicular lean soft tissue—the measure for the arms and legs—by 0.63 kg relative to tirzepatide alone.
Strength tests showed a larger contrast between groups. In the tirzepatide-only group, bench-press, lat-pulldown and knee-extension strength fell by 4.09 kg, 4.42 kg and 4.42 kg, respectively. In the exercise group, those measures rose by 4.68 kg, 8.58 kg and 5.88 kg. These results show that the training programme improved measured strength while participants were losing weight; the trial did not find that it added to tirzepatide’s effects on weight or fat loss.
Who the findings apply to
Participants were adults aged 50–70 who were initially sedentary. They had obesity, or overweight with a weight-related condition; people with diabetes or cardiovascular disease were excluded. The supervised, centre-based programme had 91% average adherence, and 111 of the 120 participants completed the trial.
The findings therefore apply most directly to a selected group receiving a closely supervised exercise programme, rather than to every person taking tirzepatide. DXA measurements also cannot separate muscle from all other lean tissue. The study supports resistance exercise as a way to limit lean-tissue loss and improve strength during treatment, but follow-up would be needed to determine whether these changes affect longer-term mobility or other health outcomes.