Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.

Horn DB, Ryan DH, Kis SG, Alves B, Mu Y, Kim SG, Aberle J, Bain SC, Allen S, Sarker E, Wu Q, Stefanski A, Jouravskaya I

Lancet (London, England)20 Nov 2025Cited by 20 (Europe PMC)

PMID41275875DOI10.1016/s0140-6736(25)02165-8PepBankPUB-41275875

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with overweight or obesity and type 2 diabetes, orforglipron 12 mg reduced bodyweight more than placebo at week 72.
In plain wordsIn adults with type 2 diabetes, orforglipron 12 mg reduced bodyweight more than placebo.
Peptide
Orforglipron
Outcome
DecreaseBodyweight change with 12 mg
Study
n = 962
Comparator
placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
12 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Bodyweight change
−7%
12 mg
Bodyweight change 95% CI
−7.8 to −6.2%
12 mg, 95% CI
Estimated treatment difference
−4.5 percentage points
versus placebo
Estimated treatment difference 95% CI
−5.5 to −3.6 percentage points
versus placebo, 95% CI
Bodyweight change
−2.5%
placebo
Bodyweight change 95% CI
−3 to −1.9%
placebo, 95% CI
P value for bodyweight change versus placebo
< 0.0001 p value
12 mg orforglipron versus placebo, baseline to week 72, treatment regimen estimand
Source sentences
Summary
-7·0% (-7·8 to -6·2) with 12 mg (ETD -4·5 [-5·5 to -3·6]; p<0·0001),
3 context sentences(design, population, supporting numbers)
Summary · context
versus -2·5% (-3·0 to -1·9) with placebo (all p<0·0001 compared with placebo).
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587502
02HumanRandomized controlled trialEfficacy outcome
In adults with overweight or obesity and type 2 diabetes, orforglipron 6 mg reduced bodyweight more than placebo at week 72.
In plain wordsIn adults with type 2 diabetes, orforglipron 6 mg reduced bodyweight more than placebo.
Peptide
Orforglipron
Outcome
DecreaseBodyweight change with 6 mg
Study
n = 959
Comparator
placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
6 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Bodyweight change
−5.1%
6 mg
Bodyweight change 95% CI
−6 to −4.2%
6 mg, 95% CI
Estimated treatment difference
−2.7 percentage points
versus placebo
Estimated treatment difference 95% CI
−3.7 to −1.6 percentage points
versus placebo, 95% CI
Bodyweight change
−2.5%
placebo
Bodyweight change 95% CI
−3 to −1.9%
placebo, 95% CI
P value for bodyweight change versus placebo
< 0.0001 p value
6 mg orforglipron versus placebo, baseline to week 72, treatment regimen estimand
Source sentences
Summary
For the treatment regimen estimand, the mean percent change in bodyweight from baseline to week 72 was -5·1% (95% CI -6·0 to -4·2) with 6 mg (estimated treatment difference [ETD] -2·7 [95% CI -3·7 to -1·6]; p<0·0001),
3 context sentences(design, population, supporting numbers)
Summary · context
versus -2·5% (-3·0 to -1·9) with placebo (all p<0·0001 compared with placebo).
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587501
03HumanRandomized controlled trialEfficacy outcome
In adults with overweight or obesity and type 2 diabetes, orforglipron 36 mg reduced bodyweight more than placebo at week 72.
In plain wordsIn adults with type 2 diabetes, orforglipron 36 mg reduced bodyweight more than placebo.
Peptide
Orforglipron
Outcome
DecreaseBodyweight change with 36 mg
Study
n = 952
Comparator
placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
36 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Bodyweight change
−9.6%
36 mg
Bodyweight change 95% CI
−10.5 to −8.7%
36 mg, 95% CI
Estimated treatment difference
−7.1 percentage points
versus placebo
Estimated treatment difference 95% CI
−8.2 to −6.1 percentage points
versus placebo, 95% CI
Bodyweight change
−2.5%
placebo
Bodyweight change 95% CI
−3 to −1.9%
placebo, 95% CI
Bodyweight change p value
< 0.0001 p value
36 mg orforglipron versus placebo, baseline to week 72, treatment regimen estimand
Source sentences
Summary
and -9·6% (-10·5 to -8·7) with 36 mg orforglipron (ETD -7·1 [-8·2 to -6·1]; p<0·0001),
3 context sentences(design, population, supporting numbers)
Summary · context
versus -2·5% (-3·0 to -1·9) with placebo (all p<0·0001 compared with placebo).
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587503
04HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity and type 2 diabetes, six deaths were reported with orforglipron and four with placebo.
In plain wordsIn adults with type 2 diabetes, six deaths were reported with orforglipron and four with placebo.
Peptide
Orforglipron
Outcome
Not applicableDeaths in orforglipron arms
Study
n = 1,613
Comparator
placebo
Outcome group
Mortality · Whole body
Studied dose
6 mg, 12 mg, or 36 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Deaths
6 participants
orforglipron groups
Deaths
4 participants
placebo
Deaths
10 participants
all study arms
Source sentences
Summary
Ten deaths were reported during the study: six with orforglipron and four with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Summary · context
From June 5, 2023, to Feb 15, 2024, 2859 participants were screened, and 1613 (757 [46·9%] female) were randomly assigned,
Report a problemFND-4127587508
05HumanRandomized controlled trialEfficacy outcome
In adults with overweight or obesity and type 2 diabetes, HbA1c significantly improved with orforglipron.
In plain wordsIn adults with type 2 diabetes, orforglipron improved the reported long-term blood sugar measure.
Peptide
Orforglipron
Outcome
DecreaseHbA1c
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
6 mg, 12 mg or 36 mg once daily · oral · 72 weeksAs given in this study (human).
Source sentences
Summary
All prespecified weight and cardiometabolic measures including HbA_1c statistically significantly improved with orforglipron.
2 context sentences(design, population, supporting numbers)
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587505
06HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity and type 2 diabetes, adverse-event discontinuations were higher with orforglipron than placebo.
In plain wordsIn adults with type 2 diabetes, adverse events caused more treatment discontinuations with orforglipron than placebo.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuations due to adverse events
Study
n: not reported in source
Comparator
placebo
Outcome group
Adverse events · Whole body
Studied dose
6 mg, 12 mg or 36 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Adverse-event discontinuations
6.1 to 9.9%
orforglipron
Adverse-event discontinuations
4.1%
placebo
Source sentences
Summary
Treatment discontinuations due to adverse events (mainly gastrointestinal-related) were higher for orforglipron (6·1-9·9%) versus placebo (4·1%).
2 context sentences(design, population, supporting numbers)
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587506
07HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity and type 2 diabetes, common orforglipron adverse events were mild-to-moderate gastrointestinal events, predominantly during dose escalation.
In plain wordsIn adults with type 2 diabetes, common orforglipron adverse events were mild-to-moderate digestive events, mainly during dose escalation.
Peptide
Orforglipron
Outcome
Direction not reportedGastrointestinal adverse events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
6 mg, 12 mg, or 36 mg once daily · oral · 72 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events with orforglipron were mild-to-moderate gastrointestinal events, predominantly occurring during dose escalation.
2 context sentences(design, population, supporting numbers)
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587507
08HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity and type 2 diabetes, investigators deemed all deaths unrelated to study treatment except one in the placebo group and one in the 12 mg orforglipron group, for which no treatment-related association was reported.
In plain wordsIn diabetic adults, investigators judged deaths unrelated except one placebo and one 12 mg orforglipron case. No treatment association was reported for orforglipron.
Peptide
Orforglipron
Outcome
Not applicableDeath attribution
Study
n: not reported in source
Outcome group
Mortality · Whole body
Studied dose
12 mg once daily · oral · 72 weeksAs given in this study (human).
Measurements
Deaths not deemed unrelated to treatment
1 participants
12 mg orforglipron
Deaths not deemed unrelated to treatment
1 participants
placebo
Source sentences
Summary
Investigators deemed all deaths unrelated to the study treatment, except for one case in the placebo group and one case in the 12 mg orforglipron group.
3 context sentences(design, population, supporting numbers)
Summary · context
For the case in the orforglipron group, no treatment-related association was reported.
Summary · context
This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries.
Summary · context
Participants with a BMI of 27 kg/m² or higher and glycated haemoglobin (HbA_1c) of 7-10% (53-86 mmol/mol)
Report a problemFND-4127587509

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 · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT05872620

A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 Diabetes

Eli Lilly and Companyn = 1,6135 Jun 2023 to 8 Aug 2025

Obesity · Overweight · Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 4 Sept 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.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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