Lancet (London, England)May 12, 2026

Tirzepatide for keeping off weight after loss in people with obesity in the USA

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated May 13, 2026

Abstract

The model-based estimate showed a 21.9% reduction in bodyweight from baseline to week 112 for adults continuing tirzepatide at the maximum tolerated dose.

Continuing tirzepatide at the maximum tolerated dose resulted in a greater bodyweight reduction compared to reducing the dose or switching to placebo.
Participants on 5 mg tirzepatide experienced a 16.6% reduction in bodyweight, while those on placebo had a 9.9% reduction.
Among participants who regained at least 50% of lost bodyweight, a higher percentage received rescue therapy in the placebo group (67%) compared to those on maximum tolerated dose (8%) and 5 mg tirzepatide (25%).
Gastrointestinal events were the most common adverse effects associated with tirzepatide, primarily during dose escalation.

Simplified

BACKGROUND: Obesity treatment improves long-term health and quality of life outcomes. Weight reduction and its maintenance play an important role in achieving these goals. We evaluated the efficacy and safety of continuing tirzepatide at the maximum tolerated dose (MTD) or lowering the dose to 5 mg compared with switching to placebo on the maintenance of bodyweight reduction obtained with tirzepatide MTD in adults with obesity.

METHODS: This phase 3b, placebo-controlled, 112-week trial, including a 60-week open-label weight-loss period and a 52-week, double-blind weight maintenance period, was conducted across 20 sites in the USA. After completing the initial weight-loss period with once weekly subcutaneous tirzepatide at the MTD (10 mg or 15 mg), adults (aged ≥18 years) with a BMI of 30 kg/mand above or 27 kg/mand above with one or more weight-related comorbidity, and a history of at least one self-reported unsuccessful dietary effort to lose bodyweight were randomly assigned in a 3:3:2 ratio to continue tirzepatide MTD, reduce to tirzepatide 5 mg, or switch to placebo for an additional 52 weeks. Starting at week 84 (24 weeks after random allocation), participants could receive rescue tirzepatide if their weight regain exceeded 50%. The primary endpoint was the percentage change in bodyweight from baseline to week 112. The primary estimand was the modified treatment-regimen estimand, which assumed that participants who initiated rescue tirzepatide would not have gained further benefit from their assigned study treatment and included all randomly allocated participants, regardless of treatment discontinuation or initiation of prohibited medications. The efficacy estimand was supportive. Safety was assessed in all participants who received at least one dose of study drug. This completed trial was registered at ClinicalTrials.gov (NCT06047548). 2 2

FINDINGS: From Sept 20, 2023, to Jan 20, 2026, 441 patients were enrolled in and took at least one dose of study treatment during the weight-loss period, with 378 participants randomly allocated at week 60 (140 to tirzepatide MTD; 144 to dose-reduction to 5 mg tirzepatide; and 94 to placebo). 372 received at least one dose of study drug during the weight maintenance period (139 for tirzepatide MTD; 142 for 5 mg tirzepatide; and 91 for placebo). 345 (91%) of 378 participants completed the study. The majority of participants were White (67%); 288 (65%) participants were female and 153 (35%) were male; and the mean age was 46·6 years (SD 13·0). At baseline, participants had a mean bodyweight of 113·8 kg (SD 27·0), a BMI of 40·1 kg/m(SD 8·1), and HbA5·64% (SD 0·4; 38·2 mmol/mol [SD 4·0]). The model-based estimate percent change in bodyweight from baseline to week 112 was -21·9% (95% CI -23·5 to -20·3) with MTD (estimated treatment difference [ETD] -12·0% [95% CI -13s·8 to -10·1]), -16·6% (95% CI -18·0 to -15·1) with 5 mg tirzepatide (ETD -6·6 [95% CI -8·3 to -5·0]), versus -9·9% (95% CI -11·1 to -8·8) with placebo (p<0·0001 for all comparisons). Among participants who regained at least 50% of lost bodyweight, observed means were 11 (8%) of 138, 35 (25%) of 142, and 60 (67%) of 90 participants received rescue therapy in the tirzepatide MTD, 5 mg tirzepatide, and placebo, respectively. The most common adverse events with tirzepatide were gastrointestinal events, which were mostly mild to moderate in severity and mostly occurred during dose escalation. 2 1c

INTERPRETATION: In adults with obesity, long-term treatment is often necessary to maintain bodyweight reduction and its associated cardiometabolic benefits. In the SURMOUNT-MAINTAIN trial, continuing tirzepatide at MTD maintained bodyweight reduction and health-related benefits. Reducing to 5 mg tirzepatide might provide a valuable alternative to discontinuation, although individuals' treatment response might vary. Together, these findings support the importance of ongoing therapy for long-term obesity management and provide evidence to inform individualised, patient-centred obesity care.

FUNDING: Eli Lilly.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declaration of interests DBH has acted as a consultant and speaker for Eli Lilly and Company and Novo Nordisk; has served as a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Kailera, Roche, and Zealand; and has received institutional research funding from Eli Lilly and Company, KVK Tech, Novo Nordisk, and Weight Watchers. LJA reports receiving consulting fees from Amgen, Atria, Boehringer Ingelheim, CinFina Pharma, Corteria, Currax Pharma, Eli Lilly and Company, Enterin, Helicore Biopharma, Jamieson Wellness, Juvena Therapeutics, Kallyope, MBX Bioscience, Novartis, Novo Nordisk, Penguin Bio, Pfizer, Prosciento, Senda Biosciences, Skye Bio, Summit Clinical, Syntis Bio, Verdiva, Veru Pharmaceuticals, and Zealand Pharmaceuticals; receiving lecture fees from Boehringer Ingelheim, Jamieson Wellness, Pfizer, Skye Bioscience, and Zealand Pharmaceuticals; receiving institutional research funding from Eli Lilly and Company, Novo Nordisk, Skye Bioscience, and Viking Therapeutics; having equity interests in Clic Bio, ERX Pharmaceuticals, Flyte Health, Jamieson Wellness, Juvena Therapeutics, Kallyope, MBX Bioscience, Mediflix, Metsera, Penguin Bio, Skye Bio, Syntis Bio, Verdiva, and Veru Pharmaceuticals; serving on a board of directors for ERX Pharmaceuticals, Flyte Health and Jamieson Wellness; receiving travel support from Eli Lilly, Jamieson Wellness, Novo Nordisk, Pfizer, and Zealand Pharma; and reports patents pending with Flyte Health. SW reports receiving non-financial support from Eli Lilly during the conduct of the study and personal fees from AbbVie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, i2o Therapeutics, Merck, Metsera, NGX, Novo Nordisk, and Regeneron outside the submitted work; has served on an advisory board for Boehringer Ingelheim; holds a leadership role for Obesity Canada and Obesity Society; and has received medical writing support from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. HEB's research site institution has received research grants from 89Bio, AbbVie, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, AstraZeneca, Bioage, Biohaven, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, Genentec, GlaxoSmithKline, Graviton, HighTide, Home Access, Horizon, Ionis, Kailera, Kallyope, LG-Chem, Marea, Madrigal, Marea, Merck, Metsera, Mineralys, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, Tern, TIMI, Veru, Viking, Vivus, and Zomagen. HEB has served as an advisor (eg, executive or national committee member or protocol or drug development advisor) for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Eli Lilly, Eva Pharma, Kiniksa, HighTide, Nestle, Novo Nordisk, Regeneron, Rivus, Veru, Zomagen, and ZyVersa; reports receiving honoraria fees from the American Society for Preventive Cardiology, National Lipid Association, and Obesity Medicine Association; and holds a leadership role as President and Chief Science Officer of the Obesity Medicine Association and as Editor-in-Chief of Obesity Pillars. CWlR reports receiving payments to their institution from Anabio, the Health Research Board, the Irish Research Council, and the Science Foundation Ireland; reports receiving consulting fees from AbbVie, Altimmune, Amgen, Arrowhead, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GI Dynamics, Gila Pharmaceuticals, Herbalife, Irish life Health, Johnson & Johnson, Keyron, Metsera, Novo Nordisk, Nymble, Olympus, and Roche; reports receiving payments for presentations from Boehringer Ingelheim, Currax Pharmaceuticals, Eli Lilly, and Rhythm Pharmaceuticals; reports travel support from Boehringer Ingelheim, Eli Lilly and Company, Herbalife, Johnson & Johnson, and Novo Nordisk; holds a leadership position at the Irish Society for Nutrition and Metabolism; is a shareholder of Metsera and Nymble; and is co-owner of Beyond BMI and My Best Weight. RS declares no competing interests. EGV, ADA, SD, JPD, AR, LCG, and CJL are employees and shareholders of Eli Lilly.

PubMed

Tirzepatide for keeping off weight after loss in people with obesity in the USA

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the glp-1 therapies brief