Weight reduction over time in tirzepatide-treated participants by early weight loss response: Post hoc analysis in SURMOUNT-1

Diabetes Obes Metab. 2025 Sep;27(9):5064-5071. doi: 10.1111/dom.16554. Epub 2025 Jul 17.

Abstract

Aims: The objective was to assess weight reduction at Weeks 24 and 72 in participants treated with tirzepatide based on weight reduction response after 12 weeks of treatment in the SURMOUNT-1 trial.

Materials and methods: This post hoc analysis included participants treated with tirzepatide who received ≥75% of the assigned treatment doses and had weight measurements at Weeks 0, 12, 24 and 72. Participants were categorized based on the 12-week response to tirzepatide: late responders (<5% weight reduction at Week 12) or early responders (≥5% weight reduction at Week 12).

Results: A total of 1545 participants were included in the analyses, with 278 (18%) categorized as late responders and 1267 (82%) categorized as early responders. At baseline, late responders compared to early responders were more likely to be male (45% vs. 30%) and had higher body weight (110.2 vs. 103.6 kg), body mass index (BMI) (39.1 vs. 37.7 kg/m2) and waist circumference (117.5 vs. 113.4 cm). At the end of dose titration, Week 24, 194 (70%) late responders achieved ≥5% body weight reduction. At Week 72, 250 (90%) late responders achieved ≥5% body weight reduction. The mean time to reach 5% weight reduction for late responders was 24.8 ± 12.7 weeks. Higher doses of tirzepatide were associated with higher proportions of participants achieving various weight reduction thresholds at Weeks 24 and 72.

Conclusions: Among late responders to tirzepatide, the vast majority (90%) achieved 5% or more weight reduction at Week 72. This finding suggests that extending treatment well beyond 12 weeks may allow additional patients to achieve clinically meaningful weight reduction.

Trial registration: ClinicalTrials.gov, identifier: NCT04184622, available at http://www.

Clinicaltrials: gov/.

Keywords: response; tirzepatide.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Obesity Agents* / administration & dosage
  • Anti-Obesity Agents* / adverse effects
  • Body Mass Index
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glucagon-Like Peptide-1 Receptor Agonists* / administration & dosage
  • Glucagon-Like Peptide-1 Receptor Agonists* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Obesity* / drug therapy
  • Time Factors
  • Tirzepatide
  • Treatment Outcome
  • Waist Circumference
  • Weight Loss* / drug effects

Substances

  • Anti-Obesity Agents
  • Tirzepatide
  • Glucagon-Like Peptide-1 Receptor Agonists

Associated data

  • ClinicalTrials.gov/NCT04184622

Grants and funding