Resistance exercise to attenuate lean mass loss during tirzepatide therapy for obesity: a randomized controlled trial
Authors' conclusion
In conclusion, resistance exercise training attenuated loss of total lean soft tissue mass, representing an effective adjunct to tirzepatide anti-obesity therapy.
Study context
- Population
- Adults with overweight or obesity treated with tirzepatideadults treated with tirzepatide and randomized
- Participants
- 120 adults
- Comparison
- Adding resistance exercise (REx) to tirzepatide (T) vs tirzepatide with usual activities for 40 weeks
- Primary endpoint
- Primary outcomes: loss of total fat mass and loss of total lean soft tissue mass
- Follow-up
- 40 weeks
Primary result
As reported in the abstract
T
- Total fat mass
- −17.19 kg
- Total lean soft tissue mass
- −4.67 kg
T+REx
- Total fat mass
- −17.98 kg
- Total lean soft tissue mass
- −3.57 kg
Total fat mass
T−17.19 kg
T+REx−17.98 kg
Total lean soft tissue mass
T−4.67 kg
T+REx−3.57 kg
T+REx vs TEstimate (95% CI)P value
Loss of total fat mass was similar
between-group difference, total fat mass −0.77 kg(−2.14 kg to 0.60 kg)
P = 0.700Resistance exercise reduced loss of total lean soft tissue mass
between-group difference, total lean soft tissue mass 1.09 kg(0.43–1.75)
P < 0.001Further findings
kg
| Outcome | T | T+REx | P value |
|---|---|---|---|
| Weight lossWeight loss achieved was similar | −22.61 | −22.28 | P = 0.694 |
| Loss of appendicular lean soft tissue mass (related endpoint) | −3.55 | −2.92 | P < 0.001 |
| Upper and lower body muscle strengthStrength decreased with tirzepatide but increased with T+REx | all P < 0.001 versus tirzepatide | ||
| Bench press | −4.09 | +4.68 | |
| Lat pulldown | −4.42 | +8.58 | |
| Knee extension | −4.42 | +5.88 |
- Loss of appendicular lean soft tissue mass (related endpoint): resistance exercise reduced loss of appendicular lean soft tissue mass
Adherence to resistance exercise
- Adherence to resistance exercise
- 91%
Safety
Safety and tolerability of tirzepatide
- Tirzepatide was safe, and most participants tolerated up-titration to 15 mg weekly
Original publication
Resistance exercise to attenuate lean mass loss during tirzepatide therapy for obesity: a randomized controlled trial. Nat Med. Published 9 November 2026. doi:10.
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