Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials
Authors' conclusion
In this post hoc analysis of 3 randomized clinical trials for participants taking at least 1 concomitant WI medication, tirzepatide treatment was associated with weight loss comparable with the primary study results. These findings suggest that people with overweight or obesity who require treatment with WI medications may be able to achieve clinically meaningful weight reduction with tirzepatide.
Study context
- Population
- Participants with overweight or obesity in SURMOUNT-1, −3 and −4 who started ≥1 weight-inducing (WI) medication for ≥3 months (≥1 week for oral corticosteroids) during the trial3 trials
- Comparison
- Tirzepatide vs placebo in participants taking concomitant WI medications
- Primary endpoint
- Percentage change in weight (mixed model of repeated measures, efficacy analysis sets)
- Follow-up
- Week 0 to week 72 or week 88
Methodological detailsphase 3, modified intent-to-treat population, Statistical analysis July to December 2025
- Phase 3
- Modified intent-to-treat population
- Statistical analysis July to December 2025
Primary result
As reported in the abstract
Mean % weight change vs placebo with WI medication use · randomization to 72 weeks (SURMOUNT-1, -3); 88 weeks (SURMOUNT-4)
Each group vs placeboMean percentage weight change (95% CI)
Tirzepatide 5 mg (SURMOUNT-1)72 weeks
−13.3%(−16.0% to −10.7%)
Tirzepatide 15 mg (SURMOUNT-1)72 weeks
−21.3%(−23.9% to −18.7%)
Tirzepatide maximum tolerated dose (SURMOUNT-3)72 weeks
−26.1%(−30.0% to −22.3%)
Tirzepatide maximum tolerated dose (SURMOUNT-4)88 weeks
−18.6%(−20.9% to −16.3%)
Further findings
Use of ≥1 WI medication
- SURMOUNT-1
- 17.4% [442 of 2539]
- SURMOUNT-3
- 17.3% [100 of 579]
- SURMOUNT-4
- 20.0% [134 of 670]
Taking 1 nonsteroid WI medication; using ≥3 medications
- 1 nonsteroid WI medication, SURMOUNT-1
- 72.9% (322 of 442)
- 1 nonsteroid WI medication, SURMOUNT-3
- 68.0% (68 of 100)
- 1 nonsteroid WI medication, SURMOUNT-4
- 64.9% (87 of 134)
- ≥3 medications, SURMOUNT-1
- 2.0% (9 of 442)
- ≥3 medications, SURMOUNT-3
- 3.0% (3 of 100)
- ≥3 medications, SURMOUNT-4
- 2.2% (3 of 134)
Mean (SD) duration of nonsteroid WI medication
Weeks
- SURMOUNT-1
- 50.9 (28.8)
- SURMOUNT-3
- 50.9 (29.3)
- SURMOUNT-4
- 58.1 (34.9)
Original publication
Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials. JAMA Netw Open. Published 2 March 2026. doi:10.
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