Audience: Clinicians. Published 11 November 2026 (AEDT). Study published: 9 November 2026 (Nature Medicine, peer reviewed, open access).
Study
T-REx (ACTRN12623001236684) was a single-centre, open-label RCT in Perth. 120 sedentary adults aged 50–70 (men and post-menopausal women) with BMI ≥30, or ≥27 with a weight-related comorbidity, without diabetes or cardiovascular disease and not on statins or antihypertensives, received supervised weekly tirzepatide titrated towards 15 mg (78 finished on 15 mg). They were randomised to three 1-hour AEP-supervised progressive resistance sessions weekly (n=59) or usual activities (n=61) for 40 weeks. Co-primary outcomes were DXA fat and lean soft tissue mass; analysis was intention-to-treat.
Results
Weight loss was similar (−22.61 vs −22.28 kg), as was fat loss (difference −0.77 kg, 95% CI −2.14 to 0.60). Lean soft tissue loss was smaller with training (−3.57 vs −4.67 kg; difference 1.09 kg, 95% CI 0.43–1.75). Bench press, lat pulldown and knee extension fell 8.4%, 6.5% and 9.0% with tirzepatide alone but rose 10.7%, 15.7% and 17.5% with training (all P<0.001). Exercise adherence was 91%; 111/120 completed. GI adverse events were similar between arms; six withdrew for adverse events; six serious adverse events were judged unrelated to treatment.
Limitations
Single centre, modest sample and selected, low-risk population; strength assessors were not blinded (DXA analysis was); DXA lean soft tissue is not purely muscle; no functional, falls or frailty outcomes; the registered week-56 follow-up is not yet reported. A supervised, high-adherence research program may not translate to routine care. Eli Lilly supplied tirzepatide and reviewed the draft (no content changes reported); several authors report Lilly honoraria.
Practical implications
Reasonable to discuss resistance training when starting incretin therapy for obesity, particularly in older or pre-frail patients, and to consider simple baseline function measures (e.g. grip strength, sit-to-stand), as the lead author suggested to newsGP. Evidence is for tirzepatide only; generalisation to other agents is unproven.
AI editorial summary from the full-text article; no independent expert commentary was located, and the newsGP report relies on the lead author. No clinical review by the ATM Health editorial team is claimed. General professional information, not patient-specific advice.
Sources
Green DJ et al. Nature Medicine, 9 November 2026. doi:10.1038/s41591-026-04752-5
newsGP (RACGP), 10 November 2026
ANZCTR registration ACTRN12623001236684. All accessed 11 November 2026 (AEDT).