Adults taking tirzepatide lost less lean tissue and gained muscle strength when they combined the medication with resistance training, according to a new randomized trial led by researchers at the University of Western Australia.
The findings, published November 9 in Nature Medicine, came from a 40-week trial that assigned 120 adults to either three resistance-training sessions a week or their usual activities. Everyone received tirzepatide.
Tirzepatide is the active ingredient in Mounjaro and Zepbound. In the US, Mounjaro treats type 2 diabetes, while Zepbound is approved for weight management in eligible adults. The medication acts on two hormone receptors involved in appetite and food intake.
Participants were men and postmenopausal women aged 50 to 70 who had obesity or overweight with a related health condition. They did not have type 2 diabetes. Both groups received general guidance on protein, fiber, and hydration.
Both groups lost about 22 kilograms (roughly 49 pounds). Those who trained lost an average of 3.57 kg of lean soft tissue, compared with 4.67 kg among those receiving the medication alone. The difference was approximately 1.1 kg.
Upper- and lower-body strength improved in the exercise group and declined in the medication-only group, including on tests involving the bench press and knee extension.
Why strength matters during weight loss
Lean tissue includes muscle and other nonfat tissue. Lead investigator Prof. Danny Green said treatment should aim to maintain physical function as weight falls, and urged doctors to incorporate resistance exercise into treatment.
"We now know that muscle loss can be reduced and strength increased when regular resistance training is used alongside tirzepatide treatment," Green said in a university statement.
The study tested a structured exercise program in a specific patient group. Its results cannot automatically be extended to other weight-loss drugs or exercise routines.
Zepbound's US prescribing information already specifies use alongside a reduced-calorie diet and increased physical activity. The new trial provides evidence about one particular form of that activity: resistance training.
The university said Eli Lilly supplied the medication and had no role in designing, running, or evaluating the investigator-initiated trial.
Several authors disclosed payments or advisory relationships with pharmaceutical or nutrition companies.