Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial
Authors' conclusion
In this post hoc analysis of the SURMOUNT-4 trial, among participants with obesity who achieved weight reduction with 36-week tirzepatide treatment, withdrawing tirzepatide led to 25% or greater weight regain in most participants within 1 year and was associated with a greater reversal of their initial cardiometabolic parameter improvements compared with those who maintained weight reduction. These findings underscore the importance of continued obesity treatment.
Study context
- Population
- Adults with obesity with ≥10% weight reduction after 36 wk of tirzepatide (10 or 15 mg), randomized to switch to placebo for 52 wk; 71.1% female, mean (SD) age 47.1 (12.2) y
- Participants
- 308 adults
- Comparison
- Cardiometabolic changes after tirzepatide withdrawal by degree of weight regain (<25%, 25% to <50%, 50% to <75%, ≥75%)
- <25%n = 54
- 25% to <50%n = 77
- 50% to <75%n = 103
- ≥75%n = 74
- Primary endpoint
- Change in cardiometabolic parameters on tirzepatide withdrawal by degree of weight regain (as % of weight lost wk 0–36)
- Follow-up
- Week 36 to week 88
Methodological detailsData collected March 2021 to May 2023; analysed February 2024 to March 2025
- Data collected March 2021 to May 2023; analysed February 2024 to March 2025
Primary result
As reported in the abstract
<25%
0.8
mean · 95% CI −1.0–2.6 · cm
25% to <50%
5.4
mean · 95% CI 4.0–6.8 · cm
50% to <75%
10.1
mean · 95% CI 8.9–11.3 · cm
≥75%
14.7
mean · 95% CI 12.7–16.7 · cm
P < 0.001
Further findings
Systolic BP change · week 36 to week 88 — between <25% and ≥75% · across weight regain categories
P = 0.002
| Outcome | <25% | 25% to <50% | 50% to <75% | ≥75% | P value |
|---|---|---|---|---|---|
| Non-HDL cholesterol change · week 36 to week 88 | −0.4% (95% CI −7.3–6.5) | 1.6% (95% CI −2.3–5.5) | 8.4% (95% CI 3.9–12.9) | 10.8% (95% CI 5.3–16.3) | |
| HbA1c change · week 36 to week 88Between <25% and ≥75% · across weight regain categories | 0.14% (95% CI 0.06–0.22) | 0.15% (95% CI 0.09–0.21) | 0.27% (95% CI 0.21–0.33) | 0.35% (95% CI 0.29–0.41) | P < 0.001 |
| Fasting insulin change · week 36 to week 88 | −4.0% (95% CI −20.7–12.7) | 15.4% (95% CI 2.3–28.5) | 46.2% (95% CI 29.5–62.9) | 26.3% (95% CI 9.6–43.0) |
<25% weight regain: week 88 vs week 36
- Waist circumference, non-HDL cholesterol and fasting insulin not significantly different from week 36
Original publication
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