Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.

Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu WS, Liu R, Li J, Fernández Landó L, Denning M, Ludwig L, Chen Y

The New England journal of medicine21 Jun 2025Cited by 71 (Europe PMC)

PMID40544435DOI10.1056/nejmoa2505669PepBankPUB-40544435

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 study10

10 results from studies that gave the peptide. 10 results from people.

01HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, orforglipron 3 mg reduced HbA1c more than placebo.
In plain wordsOrforglipron 3 mg reduced blood sugar more than placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3 mg · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change
−1.24 percentage points
3 mg
HbA1c change
−0.41 percentage points
placebo
HbA1c difference from placebo
−0.83 percentage points
3 mg versus placebo
HbA1c difference from placebo 95% CI
−1.1 to −0.56 percentage points
3 mg versus placebo
P value
< 0.001 P
all comparisons versus placebo
Source sentences
Summary
At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo.
5 context sentences(design, population, supporting numbers)
Summary · context
All three doses of orforglipron were superior to placebo with respect to the primary end point;
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Summary · context
the estimated mean difference from placebo was -0.83 percentage points (95% confidence interval [CI], -1.10 to -0.56) with the 3-mg dose,
Summary · context
(P<0.001 for all comparisons)
Report a problemFND-4054443501
02HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, orforglipron 12 mg reduced HbA1c more than placebo.
In plain wordsOrforglipron 12 mg reduced blood sugar more than placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change
−1.47 percentage points
12 mg
HbA1c change
−0.41 percentage points
placebo
HbA1c difference from placebo
−1.06 percentage points
12 mg versus placebo
HbA1c difference from placebo 95% CI
−1.33 to −0.79 percentage points
12 mg versus placebo
P value
< 0.001 P
all comparisons versus placebo
Source sentences
Summary
At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo.
5 context sentences(design, population, supporting numbers)
Summary · context
All three doses of orforglipron were superior to placebo with respect to the primary end point;
Summary · context
-1.06 percentage points (95% CI, -1.33 to -0.79) with the 12-mg dose,
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Summary · context
(P<0.001 for all comparisons)
Report a problemFND-4054443502
03HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, orforglipron 36 mg reduced HbA1c more than placebo.
In plain wordsOrforglipron 36 mg reduced blood sugar more than placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
36 mg · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change
−1.48 percentage points
36 mg
HbA1c change
−0.41 percentage points
placebo
HbA1c difference from placebo
−1.07 percentage points
36 mg versus placebo
HbA1c difference from placebo 95% CI
−1.33 to −0.81 percentage points
36 mg versus placebo
P value
< 0.001 P
all comparisons versus placebo
Source sentences
Summary
At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo.
5 context sentences(design, population, supporting numbers)
Summary · context
All three doses of orforglipron were superior to placebo with respect to the primary end point;
Summary · context
and -1.07 percentage points (95% CI, -1.33 to -0.81) with the 36-mg dose
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Summary · context
(P<0.001 for all comparisons)
Report a problemFND-4054443503
04HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, body weight decreased by 4.5% with orforglipron 3 mg versus 1.7% with placebo.
In plain wordsBody weight decreased by 4.5% with orforglipron 3 mg versus 1.7% with placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseBody weight change
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
3 mg · oral · 40 weeksAs given in this study (human).
Measurements
Body weight change
−4.5%
3 mg
Body weight change
−1.7%
placebo
Source sentences
Summary
The percent change in body weight from baseline to week 40 was -4.5% with the 3-mg dose, -5.8% with the 12-mg dose, -7.6% with the 36-mg dose, and -1.7% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443505
05HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, body weight decreased by 5.8% with orforglipron 12 mg versus 1.7% with placebo.
In plain wordsBody weight decreased by 5.8% with orforglipron 12 mg versus 1.7% with placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseBody weight change
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
12 mg · oral · 40 weeksAs given in this study (human).
Measurements
Body weight change
−5.8%
12 mg
Body weight change
−1.7%
placebo
Source sentences
Summary
The percent change in body weight from baseline to week 40 was -4.5% with the 3-mg dose, -5.8% with the 12-mg dose, -7.6% with the 36-mg dose, and -1.7% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443506
06HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, body weight decreased by 7.6% with orforglipron 36 mg versus 1.7% with placebo.
In plain wordsBody weight decreased by 7.6% with orforglipron 36 mg versus 1.7% with placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseBody weight change
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
36 mg · oral · 40 weeksAs given in this study (human).
Measurements
Body weight change
−7.6%
36 mg
Body weight change
−1.7%
placebo
Source sentences
Summary
The percent change in body weight from baseline to week 40 was -4.5% with the 3-mg dose, -5.8% with the 12-mg dose, -7.6% with the 36-mg dose, and -1.7% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443507
07HumanRandomized controlled trialSafety outcome
In early type 2 diabetes, the most common adverse events were mild-to-moderate gastrointestinal events, mostly during dose escalation.
In plain wordsIn early type 2 diabetes, the most common adverse events were mild-to-moderate digestive problems, mostly during dose escalation.
Peptide
Orforglipron
Outcome
Not applicableGastrointestinal events
Study
n = 559
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events were mild-to-moderate gastrointestinal events, most of which occurred during dose escalation.
3 context sentences(design, population, supporting numbers)
Summary · context
A total of 559 participants underwent randomization.
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443508
08HumanRandomized controlled trialSafety outcome
In early type 2 diabetes, no episodes of severe hypoglycemia were reported in the orforglipron trial.
In plain wordsNo episodes of severe low blood sugar were reported in the orforglipron trial in early type 2 diabetes.
Peptide
Orforglipron
Outcome
Not applicableSevere hypoglycemia
Study
n = 559
Outcome group
Adverse events · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
No episodes of severe hypoglycemia were reported.
3 context sentences(design, population, supporting numbers)
Summary · context
A total of 559 participants underwent randomization.
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443509
09HumanRandomized controlled trialSafety outcome
In early type 2 diabetes, adverse-event discontinuations occurred in 4.4 to 7.8% with orforglipron versus 1.4% with placebo.
In plain wordsAdverse-event discontinuations occurred in 4.4 to 7.8% with orforglipron versus 1.4% with placebo in early type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuation due to adverse events
Study
n = 559
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Measurements
Discontinuation due to adverse events
4.4 to 7.8%
orforglipron
Discontinuation due to adverse events
1.4%
placebo
Source sentences
Summary
Permanent discontinuation of orforglipron or placebo due to adverse events occurred in 4.4 to 7.8% of participants receiving orforglipron and 1.4% of participants receiving placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Summary · context
A total of 559 participants underwent randomization.
Report a problemFND-4054443510
10HumanRandomized controlled trialEfficacy outcome
In early type 2 diabetes, mean HbA1c with orforglipron was 6.5 to 6.7% at week 40.
In plain wordsMean HbA1c with orforglipron was 6.5 to 6.7% at week 40 in early type 2 diabetes.
Peptide
Orforglipron
Outcome
Not applicableHbA1c at week 40
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c at week 40
6.5 to 6.7%
orforglipron
Source sentences
Summary
The mean glycated hemoglobin level at week 40 was 6.5 to 6.7% with orforglipron.
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks.
Summary · context
Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0.
Report a problemFND-4054443504

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 postedNCT05971940

A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

Eli Lilly and Companyn = 5599 Aug 2023 to 3 Apr 2025

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 3 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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