Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.

Giorgino F, D'Souza S, Ludwig L, Kiyosue A, Ibriga H, Rha H, Denning M, Wu WS, Fernández Landó L, Tobian J

JAMA1 Aug 2026

PMID42251769DOI10.1001/jama.2026.9512PepBankPUB-42251769

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 study11

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron 12 mg lowered HbA1c by -1.88% versus -0.79% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 12 mg lowered HbA1c more than placebo.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
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
−1.88%
orforglipron 12 mg once daily, week 40
HbA1c change from baseline
−0.79%
placebo, week 40
Estimated treatment difference in HbA1c vs placebo
−1.08%
orforglipron 12 mg once daily vs placebo
95% confidence interval for estimated treatment difference in HbA1c
−1.33 to −0.83%
orforglipron 12 mg once daily vs placebo, week 40
p value for HbA1c treatment difference
< 0.001
orforglipron 12 mg once daily vs placebo, week 40
Source sentences
Summary
At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176902
02HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron 36 mg lowered HbA1c by -1.82% versus -0.79% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 36 mg lowered HbA1c more than placebo.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
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
−1.82%
orforglipron 36 mg once daily, week 40
HbA1c change from baseline
−0.79%
placebo, week 40
Estimated treatment difference in HbA1c vs placebo
−1.03%
orforglipron 36 mg once daily vs placebo
95% confidence interval for estimated treatment difference in HbA1c
−1.28 to −0.77%
orforglipron 36 mg once daily vs placebo, week 40
p value for HbA1c treatment difference
< 0.001
orforglipron 36 mg once daily vs placebo, week 40
Source sentences
Summary
At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176903
03HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron improved the proportion achieving HbA1c below 7.0% versus placebo.
In plain wordsIn adults with diabetes taking insulin glargine, more achieved the lower HbA1c target with orforglipron than placebo.
Peptide
Orforglipron
Outcome
IncreaseHbA1c below 7.0%
Study
n = 546
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
All key secondary outcomes demonstrated statistically significant differences in favor of orforglipron compared with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Key secondary outcomes were mean HbA1c change from baseline (for the 3-mg once daily dosage of orforglipron), proportion of participants achieving HbA1c targets of lower than 7.0% and 6.5% or lower, and mean body weight change and percentage change from baseline to week 40.
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176904
04HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron improved the proportion achieving HbA1c 6.5% or lower versus placebo.
In plain wordsIn adults with diabetes taking insulin glargine, more achieved the stricter HbA1c target with orforglipron than placebo.
Peptide
Orforglipron
Outcome
IncreaseHbA1c 6.5% or lower
Study
n = 546
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
All key secondary outcomes demonstrated statistically significant differences in favor of orforglipron compared with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Key secondary outcomes were mean HbA1c change from baseline (for the 3-mg once daily dosage of orforglipron), proportion of participants achieving HbA1c targets of lower than 7.0% and 6.5% or lower, and mean body weight change and percentage change from baseline to week 40.
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176905
05HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron improved mean body weight change versus placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron improved body weight change compared with placebo.
Peptide
Orforglipron
Outcome
DecreaseMean body weight change
Study
n = 546
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
All key secondary outcomes demonstrated statistically significant differences in favor of orforglipron compared with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Key secondary outcomes were mean HbA1c change from baseline (for the 3-mg once daily dosage of orforglipron), proportion of participants achieving HbA1c targets of lower than 7.0% and 6.5% or lower, and mean body weight change and percentage change from baseline to week 40.
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176906
06HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, orforglipron 3 mg lowered HbA1c by -1.58% versus -0.79% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 3 mg lowered HbA1c more than placebo.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
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
−1.58%
orforglipron 3 mg once daily, week 40
HbA1c change from baseline
−0.79%
placebo, week 40
Estimated treatment difference in HbA1c vs placebo
−0.78%
orforglipron 3 mg once daily vs placebo
95% confidence interval for estimated treatment difference in HbA1c
−1.02 to −0.55%
orforglipron 3 mg once daily vs placebo, week 40
p value for HbA1c treatment difference
< 0.001
orforglipron 3 mg once daily vs placebo, week 40
Source sentences
Summary
At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176901
07HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, body weight changed by -2.6% with orforglipron 3 mg versus 0.2% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 3 mg reduced percentage body weight more than placebo.
Peptide
Orforglipron
Outcome
DecreasePercentage body weight change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
3 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Percentage body weight change from baseline
−2.6%
orforglipron 3 mg once daily, week 40
Percentage body weight change from baseline
0.2%
placebo, week 40
Source sentences
Summary
Mean percentage body weight change from baseline was -2.6%, -4.8%, and -5.4% with orforglipron, 3 mg once daily, 12 mg once daily, and 36 mg once daily, respectively, vs 0.2% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176907
08HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, body weight changed by -4.8% with orforglipron 12 mg versus 0.2% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 12 mg reduced percentage body weight more than placebo.
Peptide
Orforglipron
Outcome
DecreasePercentage body weight change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
12 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Percentage body weight change from baseline
−4.8%
orforglipron 12 mg once daily, week 40
Percentage body weight change from baseline
0.2%
placebo, week 40
Source sentences
Summary
Mean percentage body weight change from baseline was -2.6%, -4.8%, and -5.4% with orforglipron, 3 mg once daily, 12 mg once daily, and 36 mg once daily, respectively, vs 0.2% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176908
09HumanRandomized controlled trialEfficacy outcome
In adults with T2DM taking insulin glargine, body weight changed by -5.4% with orforglipron 36 mg versus 0.2% with placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron 36 mg reduced percentage body weight more than placebo.
Peptide
Orforglipron
Outcome
DecreasePercentage body weight change
Study
n: not reported in source
Comparator
Placebo with titrated insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
36 mg once daily · oral · 40 weeksAs given in this study (human).
Measurements
Percentage body weight change from baseline
−5.4%
orforglipron 36 mg once daily, week 40
Percentage body weight change from baseline
0.2%
placebo, week 40
Source sentences
Summary
Mean percentage body weight change from baseline was -2.6%, -4.8%, and -5.4% with orforglipron, 3 mg once daily, 12 mg once daily, and 36 mg once daily, respectively, vs 0.2% with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176909
10HumanRandomized controlled trialSafety outcome
In adults with T2DM taking insulin glargine, orforglipron did not increase clinically significant hypoglycemia risk versus placebo.
In plain wordsIn adults with diabetes taking insulin glargine, orforglipron did not increase significant low blood sugar compared with placebo.
Peptide
Orforglipron
Outcome
No significant changeClinically significant hypoglycemia
Study
n = 546
Comparator
Placebo with titrated insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
Orforglipron did not increase the risk of clinically significant hypoglycemia vs placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176911
11HumanRandomized controlled trialSafety outcome
In adults with T2DM taking insulin glargine, the most frequent orforglipron adverse events were mild-to-moderate gastrointestinal events.
In plain wordsIn adults with diabetes taking insulin glargine, gut-related events were the most frequent orforglipron adverse events and were mild to moderate.
Peptide
Orforglipron
Outcome
Not applicableGastrointestinal adverse events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · oral · 40 weeksAs given in this study (human).
Source sentences
Summary
The most frequent adverse events with orforglipron were gastrointestinal (mild to moderate).
2 context sentences(design, population, supporting numbers)
Summary · context
To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control.
Summary · context
Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine.
Report a problemFND-4225176910

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 postedNCT06109311

A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor

Eli Lilly and Companyn = 54610 Nov 2023 to 15 Sept 2025

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 1 Oct 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

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