Orforglipron, an oral non-peptide glucagon-like peptide-1 receptor agonist, improves markers of β-cell function and insulin sensitivity in type 2 diabetes.

Rosenstock J, Robins DA, Duffin KL, Wilson JM, Lin Y, Banerjee H, Eyde S, Kazda C, Konig M, Mather KJ

Diabetes, obesity & metabolism14 Aug 2025Cited by 11 (Europe PMC)

PMID40808573DOI10.1111/dom.70022PepBankPUB-40808573

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 study17

17 results from studies that gave the peptide. 17 results from people.

01HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, orforglipron doses of 12 mg and higher were associated with improved beta-cell function.
In plain wordsOrforglipron doses of 12 mg and higher were linked to improved insulin-producing cell function in type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseBeta-cell function
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Orforglipron doses of 12 mg and higher were associated with improved β-cell function and insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857301
02HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, orforglipron doses of 12 mg and higher were associated with improved insulin sensitivity.
In plain wordsOrforglipron doses of 12 mg and higher were linked to improved insulin sensitivity in type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseInsulin sensitivity
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Orforglipron doses of 12 mg and higher were associated with improved β-cell function and insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857302
03HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, HOMA-B based on C-peptide increased up to 123% with orforglipron by week 4 before stabilising.
In plain wordsThe C-peptide measure of insulin-producing cell function increased up to 123% from baseline with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseHOMA-B C-peptide
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Measurements
HOMA-B increase (C-peptide)
≤ 123%
orforglipron 12 mg and higher, baseline to week 4
Source sentences
Summary
HOMA-B increased up to 123% (C-peptide) and 132% (insulin) with orforglipron doses of 12 mg and higher from baseline to week 4 before stabilising.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857303
04HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, HOMA-B based on insulin increased up to 132% with orforglipron by week 4 before stabilising.
In plain wordsThe insulin measure of insulin-producing cell function increased up to 132% from baseline with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseHOMA-B insulin
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Measurements
HOMA-B increase (insulin)
≤ 132%
orforglipron 12 mg and higher, baseline to week 4
Source sentences
Summary
HOMA-B increased up to 123% (C-peptide) and 132% (insulin) with orforglipron doses of 12 mg and higher from baseline to week 4 before stabilising.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857304
05HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, all orforglipron doses increased HOMA-B more than dulaglutide.
In plain wordsAll orforglipron doses improved the measure of insulin-producing cell function more than dulaglutide in type 2 diabetes.
Peptide
Orforglipron
Outcome
IncreaseHOMA-B versus dulaglutide
Study
n: not reported in source
Comparator
Dulaglutide
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
all doses (3, 12, 24, 36, or 45 mg) · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
HOMA-B increases were greater with all orforglipron doses than with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857305
06HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, fasting proinsulin improved with orforglipron compared with baseline.
In plain wordsFasting proinsulin improved with orforglipron compared with baseline in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedFasting proinsulin
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857306
07HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, fasting proinsulin improved more with orforglipron than dulaglutide.
In plain wordsFasting proinsulin improved more with orforglipron than dulaglutide in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedFasting proinsulin versus dulaglutide
Study
n: not reported in source
Comparator
Dulaglutide
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857307
08HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, the proinsulin/insulin ratio improved with orforglipron compared with baseline.
In plain wordsThe proinsulin/insulin ratio improved with orforglipron compared with baseline in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedProinsulin/insulin ratio
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857308
09HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, the proinsulin/insulin ratio improved more with orforglipron than dulaglutide.
In plain wordsThe proinsulin/insulin ratio improved more with orforglipron than dulaglutide in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedProinsulin/insulin ratio versus dulaglutide
Study
n: not reported in source
Comparator
Dulaglutide
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg and higher · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857309
10HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, HOMA-IR based on C-peptide decreased up to 16% with orforglipron by week 26.
In plain wordsThe C-peptide measure of insulin resistance decreased up to 16% from baseline with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHOMA-IR C-peptide
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 26 weeksAs given in this study (human).
Measurements
HOMA-IR decrease (C-peptide)
≤ 16%
orforglipron, baseline to week 26
Source sentences
Summary
HOMA-IR values decreased up to 16% (C-peptide) and 23% (insulin) with orforglipron by week 26.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857310
11HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, HOMA-IR based on insulin decreased up to 23% with orforglipron by week 26.
In plain wordsThe insulin measure of insulin resistance decreased up to 23% from baseline with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHOMA-IR insulin
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 26 weeksAs given in this study (human).
Measurements
HOMA-IR decrease (insulin)
≤ 23%
orforglipron, baseline to week 26
Source sentences
Summary
HOMA-IR values decreased up to 16% (C-peptide) and 23% (insulin) with orforglipron by week 26.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857311
12HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, only the highest orforglipron dose significantly reduced insulin-based HOMA-IR versus baseline.
In plain wordsOnly the highest orforglipron dose significantly reduced the insulin resistance measure versus baseline in type 2 diabetes.
Peptide
Orforglipron
Outcome
DecreaseHOMA-IR insulin highest dose
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
45 mg · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
Reductions in HOMA-IR (insulin) were significant versus baseline only for the highest dose.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857312
13HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, IGFBP-2 generally improved with orforglipron.
In plain wordsIGFBP-2, a marker related to insulin sensitivity, generally improved with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedIGFBP-2
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
IGFBP-2 and adiponectin, corollary biomarkers of insulin sensitivity, were generally improved with orforglipron.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857313
14HumanRandomized controlled trialEfficacy outcome
In type 2 diabetes, adiponectin generally improved with orforglipron.
In plain wordsAdiponectin, a marker related to insulin sensitivity, generally improved with orforglipron in type 2 diabetes.
Peptide
Orforglipron
Outcome
Direction not reportedAdiponectin
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 26 weeksAs given in this study (human).
Source sentences
Summary
IGFBP-2 and adiponectin, corollary biomarkers of insulin sensitivity, were generally improved with orforglipron.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857314
15HumanRandomized controlled trialEfficacy outcome
In adults with T2D, dulaglutide produced smaller HOMA-B increases than all orforglipron doses.
In plain wordsIn adults with diabetes, dulaglutide increased a beta-cell function marker less than orforglipron.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseHOMA-B increase
Study
n: not reported in source
Comparator
Orforglipron
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.5 mg · 26 weeksAs given in this study (human).
Source sentences
Summary
HOMA-B increases were greater with all orforglipron doses than with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857315
16HumanRandomized controlled trialEfficacy outcome
In adults with T2D, fasting proinsulin improved less with dulaglutide than with orforglipron doses of 12 mg and higher.
In plain wordsIn adults with diabetes, fasting proinsulin improved less with dulaglutide than with higher orforglipron doses.
Peptide
Dulaglutide (Trulicity)
Outcome
Direction not reportedFasting proinsulin improvement
Study
n: not reported in source
Comparator
Orforglipron
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.5 mg · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857316
17HumanRandomized controlled trialEfficacy outcome
In adults with T2D, the proinsulin/insulin ratio improved less with dulaglutide than with orforglipron doses of 12 mg and higher.
In plain wordsIn adults with diabetes, the proinsulin-to-insulin ratio improved less with dulaglutide than with higher orforglipron doses.
Peptide
Dulaglutide (Trulicity)
Outcome
Direction not reportedProinsulin/insulin ratio improvement
Study
n: not reported in source
Comparator
Orforglipron
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.5 mg · 26 weeksAs given in this study (human).
Source sentences
Summary
Additional β-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-4080857317

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

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 3Current
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 2
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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Orforglipron, an oral non-peptide glucagon-like peptide-1 receptor agonist, improves markers of β-cell function and insulin sensitivity in type 2 diabetes.

Summary

Results from this study17

Version history

Subjects

Publication types

MeSH terms

Keywords