Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial.

Welch M, Forst T, Jia W, Del Pino PO, Denning M, Wu WS, Li J, Liu R, Eifu M, Chen Y

Lancet (London, England)8 Jun 2026Cited by 3 (Europe PMC)

PMID42259339DOI10.1016/s0140-6736(26)00800-7PepBankPUB-42259339

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 adults with T2DM using metformin, orforglipron 3 mg reduced HbA1c more than dapagliflozin and met non-inferiority criteria.
In plain wordsIn adults with diabetes using metformin, orforglipron 3 mg lowered HbA1c more than dapagliflozin.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change from baseline
−1.23%
orforglipron 3 mg, week 40
HbA1c change from baseline
−0.81%
dapagliflozin 10 mg, week 40
Estimated treatment difference in HbA1c vs dapagliflozin
−0.42%
orforglipron 3 mg vs dapagliflozin 10 mg
Standard error of mean HbA1c change from baseline
0.08%
orforglipron 3 mg, week 40, treatment regimen estimand
Standard error of mean HbA1c change from baseline
0.07%
dapagliflozin 10 mg, week 40, treatment regimen estimand
95% confidence interval for estimated treatment difference in HbA1c
−0.62 to −0.23%
orforglipron 3 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
p value for HbA1c treatment difference
< 0.0001
orforglipron 3 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
Source sentences
Summary
Change from baseline in mean HbA_1c was -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg;
Summary
estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001)
3 context sentences(design, population, supporting numbers)
Summary · context
At week 40, for the treatment regimen estimand, all orforglipron doses were non-inferior to dapagliflozin in reducing HbA_1c.
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933901
02HumanRandomized controlled trialEfficacy outcome
In adults with T2DM using metformin, orforglipron 12 mg reduced HbA1c more than dapagliflozin and met non-inferiority criteria.
In plain wordsIn adults with diabetes using metformin, orforglipron 12 mg lowered HbA1c more than dapagliflozin.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change from baseline
−1.5%
orforglipron 12 mg, week 40
HbA1c change from baseline
−0.81%
dapagliflozin 10 mg, week 40
Estimated treatment difference in HbA1c vs dapagliflozin
−0.7%
orforglipron 12 mg vs dapagliflozin 10 mg
Standard error of mean HbA1c change from baseline
0.08%
orforglipron 12 mg, week 40, treatment regimen estimand
Standard error of mean HbA1c change from baseline
0.07%
dapagliflozin 10 mg, week 40, treatment regimen estimand
95% confidence interval for estimated treatment difference in HbA1c
−0.9 to −0.49%
orforglipron 12 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
p value for HbA1c treatment difference
< 0.0001
orforglipron 12 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
Source sentences
Summary
Change from baseline in mean HbA_1c was -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg;
Summary
estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001)
3 context sentences(design, population, supporting numbers)
Summary · context
At week 40, for the treatment regimen estimand, all orforglipron doses were non-inferior to dapagliflozin in reducing HbA_1c.
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933902
03HumanRandomized controlled trialEfficacy outcome
In adults with T2DM using metformin, orforglipron 36 mg reduced HbA1c more than dapagliflozin and met non-inferiority criteria.
In plain wordsIn adults with diabetes using metformin, orforglipron 36 mg lowered HbA1c more than dapagliflozin.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
36 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
HbA1c change from baseline
−1.56%
orforglipron 36 mg, week 40
HbA1c change from baseline
−0.81%
dapagliflozin 10 mg, week 40
Estimated treatment difference in HbA1c vs dapagliflozin
−0.75%
orforglipron 36 mg vs dapagliflozin 10 mg
Standard error of mean HbA1c change from baseline
0.09%
orforglipron 36 mg, week 40, treatment regimen estimand
Standard error of mean HbA1c change from baseline
0.07%
dapagliflozin 10 mg, week 40, treatment regimen estimand
95% confidence interval for estimated treatment difference in HbA1c
−0.96 to −0.55%
orforglipron 36 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
p value for HbA1c treatment difference
< 0.0001
orforglipron 36 mg vs dapagliflozin 10 mg, week 40, treatment regimen estimand
Source sentences
Summary
Change from baseline in mean HbA_1c was -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg;
Summary
estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001)
3 context sentences(design, population, supporting numbers)
Summary · context
At week 40, for the treatment regimen estimand, all orforglipron doses were non-inferior to dapagliflozin in reducing HbA_1c.
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933903
04HumanRandomized controlled trialSafety outcome
In adults with T2DM, no severe hypoglycaemia episode was reported during the orforglipron versus dapagliflozin trial.
In plain wordsIn adults with diabetes, no severe low blood sugar episode was reported in the orforglipron versus dapagliflozin trial.
Peptide
Orforglipron
Outcome
Not applicableSevere hypoglycaemia
Study
n = 962
Outcome group
Adverse events · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
No severe episode of hypoglycaemia was reported.
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933910
05HumanRandomized controlled trialSafety outcome
In adults with T2DM, gastrointestinal events occurred in 47% with orforglipron 3 mg versus 12% with dapagliflozin.
In plain wordsIn adults with diabetes, orforglipron 3 mg had more gut-related events than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
3 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal adverse events
47%
orforglipron 3 mg
Participants with gastrointestinal adverse events
112 participants
orforglipron 3 mg
Participants with gastrointestinal adverse events
12%
dapagliflozin 10 mg
Participants with gastrointestinal adverse events
29 participants
dapagliflozin 10 mg
Participant denominator for gastrointestinal adverse events
240 participants
orforglipron 3 mg
Participant denominator for gastrointestinal adverse events
240 participants
dapagliflozin 10 mg
Source sentences
Summary
The most frequent adverse events associated with orforglipron were mild-to-moderate gastrointestinal events, observed in 112 (47%) of 240 participants receiving orforglipron 3 mg, 112 (46%) of 241 receiving 12 mg, and 130 (54%) of 241 receiving 36 mg, versus 29 (12%) of 240 receiving dapagliflozin.
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933904
06HumanRandomized controlled trialSafety outcome
In adults with T2DM, gastrointestinal events occurred in 46% with orforglipron 12 mg versus 12% with dapagliflozin.
In plain wordsIn adults with diabetes, orforglipron 12 mg had more gut-related events than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
12 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal adverse events
46%
orforglipron 12 mg
Participants with gastrointestinal adverse events
112 participants
orforglipron 12 mg
Participants with gastrointestinal adverse events
12%
dapagliflozin 10 mg
Participants with gastrointestinal adverse events
29 participants
dapagliflozin 10 mg
Participant denominator for gastrointestinal adverse events
241 participants
orforglipron 12 mg
Participant denominator for gastrointestinal adverse events
240 participants
dapagliflozin 10 mg
Source sentences
Summary
The most frequent adverse events associated with orforglipron were mild-to-moderate gastrointestinal events, observed in 112 (47%) of 240 participants receiving orforglipron 3 mg, 112 (46%) of 241 receiving 12 mg, and 130 (54%) of 241 receiving 36 mg, versus 29 (12%) of 240 receiving dapagliflozin.
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933905
07HumanRandomized controlled trialSafety outcome
In adults with T2DM, gastrointestinal events occurred in 54% with orforglipron 36 mg versus 12% with dapagliflozin.
In plain wordsIn adults with diabetes, orforglipron 36 mg had more gut-related events than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
36 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal adverse events
54%
orforglipron 36 mg
Participants with gastrointestinal adverse events
130 participants
orforglipron 36 mg
Participants with gastrointestinal adverse events
12%
dapagliflozin 10 mg
Participants with gastrointestinal adverse events
29 participants
dapagliflozin 10 mg
Participant denominator for gastrointestinal adverse events
241 participants
orforglipron 36 mg
Participant denominator for gastrointestinal adverse events
240 participants
dapagliflozin 10 mg
Source sentences
Summary
The most frequent adverse events associated with orforglipron were mild-to-moderate gastrointestinal events, observed in 112 (47%) of 240 participants receiving orforglipron 3 mg, 112 (46%) of 241 receiving 12 mg, and 130 (54%) of 241 receiving 36 mg, versus 29 (12%) of 240 receiving dapagliflozin.
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933906
08HumanRandomized controlled trialSafety outcome
In adults with T2DM, discontinuations occurred in 15% with orforglipron 3 mg versus 6% with dapagliflozin.
In plain wordsIn adults with diabetes, more discontinued orforglipron 3 mg than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseIntervention discontinuation
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Adverse events · Whole body
Studied dose
3 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with study intervention discontinuation
15%
orforglipron 3 mg
Participants with study intervention discontinuation
35 participants
orforglipron 3 mg
Participants with study intervention discontinuation
6%
dapagliflozin 10 mg
Participants with study intervention discontinuation
14 participants
dapagliflozin 10 mg
Participant denominator for study intervention discontinuation
240 participants
orforglipron 3 mg
Participant denominator for study intervention discontinuation
240 participants
dapagliflozin 10 mg
Source sentences
Summary
More study intervention discontinuations were observed with orforglipron 3 mg (35 [15%] of 240), 12 mg (44 [18%] of 241), and 36 mg (47 [20%] of 241) than with dapagliflozin (14 [6%] of 240).
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933907
09HumanRandomized controlled trialSafety outcome
In adults with T2DM, discontinuations occurred in 18% with orforglipron 12 mg versus 6% with dapagliflozin.
In plain wordsIn adults with diabetes, more discontinued orforglipron 12 mg than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseIntervention discontinuation
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Adverse events · Whole body
Studied dose
12 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with study intervention discontinuation
18%
orforglipron 12 mg
Participants with study intervention discontinuation
44 participants
orforglipron 12 mg
Participants with study intervention discontinuation
6%
dapagliflozin 10 mg
Participants with study intervention discontinuation
14 participants
dapagliflozin 10 mg
Participant denominator for study intervention discontinuation
241 participants
orforglipron 12 mg
Participant denominator for study intervention discontinuation
240 participants
dapagliflozin 10 mg
Source sentences
Summary
More study intervention discontinuations were observed with orforglipron 3 mg (35 [15%] of 240), 12 mg (44 [18%] of 241), and 36 mg (47 [20%] of 241) than with dapagliflozin (14 [6%] of 240).
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933908
10HumanRandomized controlled trialSafety outcome
In adults with T2DM, discontinuations occurred in 20% with orforglipron 36 mg versus 6% with dapagliflozin.
In plain wordsIn adults with diabetes, more discontinued orforglipron 36 mg than dapagliflozin.
Peptide
Orforglipron
Outcome
IncreaseIntervention discontinuation
Study
n: not reported in source
Comparator
Dapagliflozin 10 mg
Outcome group
Adverse events · Whole body
Studied dose
36 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Participants with study intervention discontinuation
20%
orforglipron 36 mg
Participants with study intervention discontinuation
47 participants
orforglipron 36 mg
Participants with study intervention discontinuation
6%
dapagliflozin 10 mg
Participants with study intervention discontinuation
14 participants
dapagliflozin 10 mg
Participant denominator for study intervention discontinuation
241 participants
orforglipron 36 mg
Participant denominator for study intervention discontinuation
240 participants
dapagliflozin 10 mg
Source sentences
Summary
More study intervention discontinuations were observed with orforglipron 3 mg (35 [15%] of 240), 12 mg (44 [18%] of 241), and 36 mg (47 [20%] of 241) than with dapagliflozin (14 [6%] of 240).
2 context sentences(design, population, supporting numbers)
Summary · context
This 40-week, phase 3, multicentre, open-label (orforglipron dose-blinded), randomised study was conducted in 73 sites across six countries.
Summary · context
Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg.
Report a problemFND-4225933909

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 3NCT06192108

A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin

Eli Lilly and Companyn = 96210 Jan 2024 to 26 Sept 2025

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 20 Oct 2025

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

PepBank is a research reference. Talk to a doctor before you use any peptide.