Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Tirzepatide and Resistance Exercise training (T±REx) for obesity therapy: a randomised controlled trial. (143843)

Daniel J Green 1 , Andrew Haynes 1 , Destiny R Underwood 1 , Evangeline R Winterton 1 , Abbey A Green 1 , Robin M Daly 2 , Leanne Lester 3 , Louise H Naylor 1 , Graham S Hillis 4 , P. Gerry Fegan 5 6 7 , Bu B Yeap 5 8
  1. School of Human Sciences, University of Western Australia, Perth, WA, Australia
  2. Deakin Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC, Australia
  3. Centre for Social Impact, University of Western Australia, Perth, WA, Australia
  4. Department of Cardiology, Royal Perth Hospital, Perth, WA, Australia
  5. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia
  6. Medical School, University of Western Australia, Perth, WA, Australia
  7. Medical School, Curtin University, Perth, WA, Australia
  8. Medical School, University of Western Australia, Perth, WA, Australia

BACKGROUND

Incretin-mimetics as obesity therapy induce substantial weight and fat loss, but also decrease lean soft tissue mass, possibly impairing skeletal muscle function. Whether resistance exercise training (REx) protects muscle during incretin-induced weight loss is unclear.

METHODS

In this investigator-initiated trial, we randomized 120 adults aged 50-70 years (60 men, 60 women; BMI ≥30, or ≥27 kg/m2 with weight-related complications), to 40-weeks of centre-based, supervised and monitored progressive REx, or usual activities. All received concurrent tirzepatide (T, dose escalation to 15mg, as tolerated). The primary endpoints were changes in lean soft tissue mass, and fat mass, assessed by dual energy X-ray absorptiometry (DXA). Key secondary endpoints were regional muscle strength. Assessments were repeated every 8-weeks and intention-to-treat analysis performed using linear mixed models. 

RESULTS

Resistance exercise reduced losses in total body lean soft tissue mass (mean±SE) (T=-4.67±0.23, T+REx=-3.57±0.23 kg, P<0.001) and appendicular lean soft tissue mass (T=-3.52±0.14, T+REx=-2.94±0.14 kg, P<0.001) over 40-weeks. Both groups had similar decreases in body weight (T=-22.57±0.61, T+REx=-22.32±0.62 kg, P=0.694) and total fat mass (T=-17.91±0.51, T+REx=-17.97±0.52 kg, P=0.700). Resistance exercise (T+REx) increased upper (bench press: +4.68±0.75 kg; lat pulldown: +8.58±1.08 kg) and lower-body strength (leg extension +5.88±1.29 kg, all P<0.001), whereas tirzepatide alone decreased strength (bench press -4.09±0.75 kg; lat pulldown -4.42±1.09 kg; leg extension -4.42±1.27 kg, all P<0.001). Blood pressure, fasting glucose, insulin, HbA1c and lipids improved similarly in both groups.

CONCLUSIONS

Progressive resistance training attenuated loss of lean mass and increased muscle strength during tirzepatide therapy. This represents an effective strategy to optimise body composition and strength in older adults being treated for obesity.