Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.

Aronne LJ, Horn DB, le Roux CW, Chao AM, Ho W, Halpern B, Griffin R, Xie C, Valderas EG, Lee CJ, Ribeiro A, Hyman DM, Glass L, Xavier N

Nature medicine13 May 2026Cited by 14 (Europe PMC)

PMID42120723PMCIDPMC13375559DOI10.1038/s41591-026-04386-7PepBankPUB-42120723

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Summary

Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging. Orforglipron, a once-daily oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated weight loss efficacy, improvements in cardiometabolic risk factors, and safety generally similar to injectable GLP-1 receptor agonists. Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo. Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% (s.e.m. 4.05) of body weight reduction with orforglipron compared with an MBE of 49.2% (s.e.m. 3.92) with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval 14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52. Cohort 2 participants who achieved body weight plateau maintained an MBE of 79.3% (s.e.m. 4.42) of body weight reduction with orforglipron compared with an MBE of 37.6% (s.e.m. 7.46) with placebo, resulting in an estimated treatment difference of MBE 41.7 (95% confidence interval 24.4 to 59.0); P < 0.001; treatment-regimen estimand) at week 52. All key secondary endpoints were met. The most common adverse events were gastrointestinal effects, which were mostly mild to moderate in severity. These data demonstrate orforglipron's potential as a globally scalable option for minimizing weight changes after injectable therapy. Trial limitations include the absence of a comparator arm involving continued use of injectable obesity-management medications and the trial's 1-year duration. ClinicalTrials.gov registration: NCT06584916 .

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In previously treated participants, the orforglipron trial met all key secondary endpoints, which the abstract did not specify.
In plain wordsIn previously treated participants, the orforglipron trial met all key secondary endpoints, which the abstract did not specify.
Peptide
Orforglipron
Outcome
Direction not reportedKey secondary endpoints
Study
n: not reported in source
Analysis
Secondary
Outcome group
Overall treatment effect · Metabolic and weight
Studied dose
Dose not stated · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
All key secondary endpoints were met.
1 context sentence(design, population, supporting numbers)
Summary · context
Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo.
Show in the study text Report a problemFND-4212072303
02HumanRandomized controlled trialEfficacy outcome
In participants at weight plateau after tirzepatide, orforglipron maintained 74.7% of weight reduction versus 49.2% with placebo.
In plain wordsAfter tirzepatide, participants at weight plateau maintained more weight loss with orforglipron than placebo.
Peptide
Orforglipron
Outcome
IncreaseWeight reduction maintained after tirzepatide
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · oral · 52 weeksAs given in this study (human).
Measurements
Body weight reduction maintained (MBE)
74.7%
orforglipron, cohort 1 (previously tirzepatide), week 52
Body weight reduction maintained (MBE)
49.2%
placebo, cohort 1 (previously tirzepatide), week 52
Estimated treatment difference in maintained body weight reduction (MBE)
25.5%
orforglipron versus placebo, cohort 1, week 52
95% CI of estimated treatment difference
14.5 to 36.5%
orforglipron versus placebo, cohort 1, week 52
Source sentences
Summary
Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% (s.e.m. 4.05) of body weight reduction with orforglipron compared with an MBE of 49.2% (s.e.m. 3.92) with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval 14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52.
1 context sentence(design, population, supporting numbers)
Summary · context
Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo.
Show in the study text Report a problemFND-4212072301
03HumanRandomized controlled trialEfficacy outcome
In participants at weight plateau after semaglutide, orforglipron maintained 79.3% of weight reduction versus 37.6% with placebo.
In plain wordsAfter semaglutide, participants at weight plateau maintained more weight loss with orforglipron than placebo.
Peptide
Orforglipron
Outcome
IncreaseWeight reduction maintained after semaglutide
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · oral · 52 weeksAs given in this study (human).
Measurements
Body weight reduction maintained (MBE)
79.3%
orforglipron, cohort 2 (previously semaglutide), week 52
Body weight reduction maintained (MBE)
37.6%
placebo, cohort 2 (previously semaglutide), week 52
Estimated treatment difference in maintained body weight reduction (MBE)
41.7 MBE
orforglipron versus placebo, cohort 2, week 52
95% CI of estimated treatment difference
24.4 to 59 MBE
orforglipron versus placebo, cohort 2, week 52
Source sentences
Summary
Cohort 2 participants who achieved body weight plateau maintained an MBE of 79.3% (s.e.m. 4.42) of body weight reduction with orforglipron compared with an MBE of 37.6% (s.e.m. 7.46) with placebo, resulting in an estimated treatment difference of MBE 41.7 (95% confidence interval 24.4 to 59.0); P < 0.001; treatment-regimen estimand) at week 52.
1 context sentence(design, population, supporting numbers)
Summary · context
Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo.
Show in the study text Report a problemFND-4212072302
04HumanRandomized controlled trialSafety outcome
In previously treated participants, gastrointestinal effects were the most common adverse events and were mostly mild to moderate.
In plain wordsIn previously treated participants, the orforglipron trial reported mostly mild to moderate gastrointestinal effects as the most common adverse events.
Peptide
Orforglipron
Outcome
Direction not reportedGastrointestinal adverse effects
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events were gastrointestinal effects, which were mostly mild to moderate in severity.
1 context sentence(design, population, supporting numbers)
Summary · context
Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo.
Show in the study text Report a problemFND-4212072304

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3NCT06584916

A Study of Orforglipron for the Maintenance of Body Weight Reduction in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-MAINTAIN)

Eli Lilly and Companyn = 37613 Sept 2024 to 21 Nov 2025

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 4 Jun 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Versions 5 to 16Current
28 Oct 2026, 02:03 UTC
The same notice was added 12 times, first on 14 Oct 2026, 05:02 UTC. The status did not change between them.
Study results updated
Version 4
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Version 3
11 Oct 2026, 00:04 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC