Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial
Authors' conclusion
In the SURPASS-3 MRI substudy, in the context of significant improvements in bodyweight and fat distribution, tirzepatide treatment was associated with potentially favourable changes in muscle fat infiltration and reductions in muscle volume broadly in accordance with the general association between changes in muscle volume and bodyweight. The present findings provide additional information on the potential effect of tirzepatide on muscle health that might help health-care providers when deciding among treatment options for individual patients.
Study context
- Population
- Insulin-naive adults (≥18 years) with T2D on metformin ± SGLT2i, HbA1c 7.0–10.5%, BMI ≥25 kg/m², fatty liver index ≥60; mean age 56.0 years, mean BMI 33.4 kg/m²296 enrolled in MRI substudy
- Participants
- 246 adults
- Comparison
- Tirzepatide (5, 10 or 15 mg once weekly) vs insulin degludec; observed changes vs UK Biobank population-based estimates
- Tirzepatide 5 mgn = 63
- Tirzepatide 10 mgn = 60
- Tirzepatide 15 mgn = 67
- Insulin degludecn = 56reference
- Primary endpoint
- Changes in thigh muscle volume, muscle volume Z score and muscle fat infiltration by MRI
- Follow-up
- Baseline to week 52
Methodological detailsMRI substudy, open-label, parallel-group, phase 3, multicentre (45 sites), multinational (eight countries), post-hoc exploratory, modified intention to treat, Recruitment April 1, 2019, to Nov 15, 2019
- MRI substudy
- Open-label
- Parallel-group
- Phase 3
- Multicentre (45 sites)
- Multinational (eight countries)
- Post-hoc exploratory
- Modified intention to treat
- Recruitment April 1, 2019, to Nov 15, 2019
Primary result
As reported in the abstract
Muscle fat infiltration, mean change (pooled tirzepatide)
−0.36 percentage points
95% CI −0.48 to −0.25p<0.0001
Muscle volume, change (pooled tirzepatide)
−0.64 L
95% CI −0.74 to −0.54p<0.0001
Muscle volume Z score, change (pooled tirzepatide)
−0.22
95% CI −0.29 to −0.15p<0.0001
Further findings
| Outcome | Mean difference (L) (95% CI) | P value | |
|---|---|---|---|
| Observed vs UK Biobank population-based estimated changes · week 52Tirzepatide (pooled), observedvs Population-based estimateMuscle volume; similar to estimate | −0.04 (−0.11 to 0.03) | P = 0.22 | |
| −0.15−0.1−0.0500.05Difference, L (linear scale) |
| Outcome | Mean difference (percentage points) (95% CI) | P value | |
|---|---|---|---|
| Observed vs UK Biobank population-based estimated changes · week 52Tirzepatide (pooled), observedvs Population-based estimateMuscle fat infiltration; greater reduction than estimate | −0.42 (−0.54 to −0.31) | P < 0.0001 | |
| −1−0.500.5Difference, percentage points (linear scale) |
| Outcome | Mean difference (95% CI) | P value | |
|---|---|---|---|
| Observed vs UK Biobank population-based estimated changes · week 52Tirzepatide 15 mg, observedvs Population-based estimateMuscle volume Z score; greater reduction than estimate | −0.18 (−0.29 to −0.07) | P = 0.0016 | |
| −0.4−0.200.2Difference (linear scale) |
- Observed vs UK Biobank population-based estimated changes: UK Biobank n=2942
Original publication
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