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

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

Jamy Ard  1 , Clare J Lee  2 , Kimberly Gudzune  3 , Brandi Addison  4 , Ildiko Lingvay  5 , Dachuang Cao  2 , Casey J Mast  2 , Adam Stefanski  2 , Beverly Falcon  2 , Donna Mojdami  2
Affiliations
Clinical Trial

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

Jamy Ard et al. Diabetes Obes Metab. 2025 Sep.

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.

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Conflict of interest statement

Jamy Ard received research support from Nestle Healthcare Nutrition, Eli Lilly and Company, Boehringer Ingelheim, Epitomee, Inc., UnitedHealth Group R&D, KVKTech, WW and Novo Nordisk and is a consultant for Nestle Healthcare Nutrition, Eli Lilly and Company, Optum Labs R&D, Novo Nordisk, Intuitive, Regeneron, Brightseed, Amplifier Therapeutics, Amgen and Ingredion. Dr. Ard is an advisory board member for Novo Nordisk, Nestle Healthcare Nutrition, Eli Lilly and Company, WW and Boehringer Ingelheim. He is a member of the International Food Information Council—Assembly, The Obesity Society—President 2024, American Diabetes Association, Society of Behavioural Medicine, Roundtable on Obesity Solutions, American Society for Nutrition and American Society for Nutrition Foundation—Board of Trustees Executive Committee. Kimberly Gudzune was an Associate Professor in the Department of Medicine at the Johns Hopkins University School of Medicine and engaged in this research as a private advisor and not in her capacity as a Johns Hopkins faculty member. She received no compensation for this work. She has received personal fees for participation on advisory boards for Eli Lilly and Company and Novo Nordisk and travel support from Eli Lilly and Company and Novo Nordisk. Her former institution (Johns Hopkins) received grant funding from Novo Nordisk. Since the initial conduct of this research, Dr. Gudzune reports being an employee of the American Board of Obesity Medicine Foundation. Brandi Addison is a speaker for Eli Lilly and Company, Novo Nordisk and Corcept Therapeutics and is an advisory board member for Eli Lilly and Company. She is a member of the American Association of Clinical Endocrinology and The Obesity Society. Ildiko Lingvay received research funding (paid to institution) and/or products from Novo Nordisk, Sanofi, Boehringer‐Ingelheim, Dexcom and received research‐related consulting fees (paid to institution) from Novo Nordisk. She received advisory/consulting fees and/or other support from: AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer‐Ingelheim, Carmot, Cytoki Pharma, Eli Lilly and Company, Intercept, Janssen/J&J, Juvena, Keros Therapeutic, Inc., Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD and Zealand Pharma. Clare J. Lee, Dachuang Cao, Casey J. Mast, Adam Stefanski, Beverly Falcon and Donna Mojdami are employees and shareholders of Eli Lilly and Company.

Figures

FIGURE 1
FIGURE 1
Proportion of all tirzepatide participants achieving weight reduction targets at Week 24. The proportion of participants treated with tirzepatide who had weight reductions of at least 5%, 10%, 15%, 20% and 25% from baseline to Week 24. Error bars indicate 95% confidence intervals.
FIGURE 2
FIGURE 2
Proportion of participants achieving weight reduction targets at endpoint (Week 72). The proportion of participants treated with tirzepatide (A), tirzepatide 5 mg (B), tirzepatide 10 mg (C) and tirzepatide 15 mg (D) who had weight reductions of at least 5%, 10%, 15%, 20% and 25% from baseline to Week 72. Error bars indicate 95% confidence intervals.
FIGURE 3
FIGURE 3
The percent change in body weight from baseline to endpoint (Week 72) in all tirzepatide participants. The percent change in body weight from baseline to Week 72 according to weeks since randomization by 12‐week response subgroups with early responders further defined by degrees of weight loss (late responders, early responders 5%–10% weight reduction and early responders ≥10% weight reduction). Error bars indicate 95% confidence intervals.
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