Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial.

Rosenstock J, Yabe D, Cox D, Li J, Denning M, Wu WS, Liu R, Zhao Y

Lancet (London, England)26 Feb 2026Cited by 22 (Europe PMC)

PMID41765029DOI10.1016/s0140-6736(26)00202-3PepBankPUB-41765029

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Summary

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

Results from this study33

33 results from studies that gave the peptide. 33 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes inadequately controlled with metformin, oral semaglutide 7 mg lowered HbA1c by a mean of 1·23% from a baseline of 8·3% at week 52.
In plain wordsIn adults with type 2 diabetes, HbA1c fell on average by 1·23% over 52 weeks with oral semaglutide 7 mg.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 52, semaglutide 7 mg
Study
n = 426
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c change
−1.23%
semaglutide 7 mg
Source sentences
Summary
mean changes at week 52 from a baseline HbA_1c of 8·3%
2 context sentences(design, population, supporting numbers)
Summary · context
-1·23% (0·05) with semaglutide 7 mg
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
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02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes inadequately controlled with metformin, oral semaglutide 14 mg lowered HbA1c by a mean of 1·47% from a baseline of 8·3% at week 52.
In plain wordsIn adults with type 2 diabetes, HbA1c fell on average by 1·47% over 52 weeks with oral semaglutide 14 mg.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 52, semaglutide 14 mg
Study
n = 425
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c change
−1.47%
semaglutide 14 mg
Source sentences
Summary
-1·47% (0·06) with semaglutide 14 mg.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502902
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, mean HbA1c change with orforglipron 12 mg was -1·71% at week 52.
In plain wordsIn adults with diabetes, orforglipron 12 mg reduced HbA1c from baseline.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n = 424
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean HbA1c change from baseline at week 52
−1.71%
orforglipron 12 mg, treatment regimen estimand (SE 0.07)
Source sentences
Summary
For the treatment regimen estimand, mean changes at week 52 from a baseline HbA_1c of 8·3% were -1·71% (SE 0·07) with orforglipron 12 mg, -1·91% (0·08) with orforglipron 36 mg, -1·23% (0·05) with semaglutide 7 mg, and -1·47% (0·06) with semaglutide 14 mg.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502914
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, mean HbA1c change with orforglipron 36 mg was -1·91% at week 52.
In plain wordsIn adults with diabetes, orforglipron 36 mg reduced HbA1c from baseline.
Peptide
Orforglipron
Outcome
DecreaseHbA1c change
Study
n = 423
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean HbA1c change from baseline at week 52
−1.91%
orforglipron 36 mg, treatment regimen estimand (SE 0.08)
Source sentences
Summary
For the treatment regimen estimand, mean changes at week 52 from a baseline HbA_1c of 8·3% were -1·71% (SE 0·07) with orforglipron 12 mg, -1·91% (0·08) with orforglipron 36 mg, -1·23% (0·05) with semaglutide 7 mg, and -1·47% (0·06) with semaglutide 14 mg.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
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05HumanRandomized controlled trialEfficacy outcome
HbA1c reduction at week 52 was smaller with oral semaglutide 7 mg than with orforglipron 12 mg (treatment difference -0·48% for orforglipron versus semaglutide).
In plain wordsOrforglipron 12 mg lowered HbA1c more than oral semaglutide 7 mg over 52 weeks in adults with type 2 diabetes.
Peptide
Semaglutide
Outcome
IncreaseHbA1c change versus orforglipron 12 mg, semaglutide 7 mg
Study
n: not reported in source
Comparator
Orforglipron 12 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
treatment difference (orforglipron 12 mg minus semaglutide 7 mg)
−0.48%
week 52
Source sentences
Summary
-0·48% (95% CI -0·65 to -0·31; p<0·0001) for orforglipron 12 mg versus semaglutide 7 mg
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502903
06HumanRandomized controlled trialEfficacy outcome
HbA1c reduction at week 52 was smaller with oral semaglutide 14 mg than with orforglipron 36 mg (treatment difference -0·44% for orforglipron versus semaglutide).
In plain wordsOrforglipron 36 mg lowered HbA1c more than oral semaglutide 14 mg over 52 weeks in adults with type 2 diabetes.
Peptide
Semaglutide
Outcome
IncreaseHbA1c change versus orforglipron 36 mg, semaglutide 14 mg
Study
n: not reported in source
Comparator
Orforglipron 36 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
treatment difference (orforglipron 36 mg minus semaglutide 14 mg)
−0.44%
week 52
Source sentences
Summary
-0·44% (-0·62 to -0·26; p<0·0001) for orforglipron 36 mg versus semaglutide 14 mg
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502904
07HumanRandomized controlled trialEfficacy outcome
In adults with diabetes, orforglipron 12 mg reduced HbA1c more than semaglutide 7 mg, with a difference of -0·48%.
In plain wordsIn adults with diabetes, orforglipron 12 mg reduced HbA1c more than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
DecreaseHbA1c treatment difference
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c estimated treatment difference
−0.48%
orforglipron 12 mg versus semaglutide 7 mg
95% CI
−0.65 to −0.31%
orforglipron 12 mg versus semaglutide 7 mg
p-value
< 0.0001
orforglipron 12 mg versus semaglutide 7 mg
Source sentences
Summary
Estimated treatment differences were -0·48% (95% CI -0·65 to -0·31; p<0·0001) for orforglipron 12 mg versus semaglutide 7 mg;
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502916
08HumanRandomized controlled trialEfficacy outcome
In adults with diabetes, orforglipron 36 mg reduced HbA1c more than semaglutide 14 mg, with a difference of -0·44%.
In plain wordsIn adults with diabetes, orforglipron 36 mg reduced HbA1c more than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
DecreaseHbA1c treatment difference
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c estimated treatment difference
−0.44%
orforglipron 36 mg versus semaglutide 14 mg
CI
−0.62 to −0.26%
orforglipron 36 mg versus semaglutide 14 mg
p-value
< 0.0001
orforglipron 36 mg versus semaglutide 14 mg
Source sentences
Summary
-0·44% (-0·62 to -0·26; p<0·0001) for orforglipron 36 mg versus semaglutide 14 mg;
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502917
09HumanRandomized controlled trialSafety outcome
Gastrointestinal events were the most frequent adverse events with oral semaglutide 7 mg: 157 of 426 participants (37%), most mild to moderate.
In plain wordsAbout 37% of people on oral semaglutide 7 mg had stomach or gut side effects, most of them mild to moderate.
Peptide
Semaglutide
Outcome
Not applicableGastrointestinal adverse events, semaglutide 7 mg
Study
n = 426
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
participants with gastrointestinal events
157 participants
semaglutide 7 mg
proportion
37%
semaglutide 7 mg
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502907
10HumanRandomized controlled trialSafety outcome
Fewer participants discontinued treatment due to adverse events with oral semaglutide 7 mg (19, 4%) than with orforglipron.
In plain wordsFewer people stopped oral semaglutide 7 mg because of side effects (4%) than stopped orforglipron.
Peptide
Semaglutide
Outcome
DecreaseDiscontinuation due to adverse events, semaglutide 7 mg
Study
n = 426
Comparator
Orforglipron
Outcome group
Adverse events · Whole body
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
discontinuations
19 participants
semaglutide 7 mg
proportion
4%
semaglutide 7 mg
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg)
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502909
11HumanRandomized controlled trialSafety outcome
Mean pulse rate increased by 1·0 bpm with oral semaglutide 7 mg, less than with orforglipron.
In plain wordsPulse rate rose by 1·0 beat per minute on oral semaglutide 7 mg, a smaller rise than with orforglipron.
Peptide
Semaglutide
Outcome
IncreasePulse rate increase, semaglutide 7 mg
Study
n = 426
Comparator
Orforglipron
Outcome group
Adverse events · Cardiovascular
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
mean pulse rate increase
1 bpm
semaglutide 7 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502911
12HumanRandomized controlled trialSafety outcome
Two deaths occurred in the oral semaglutide 7 mg group during the study.
In plain wordsTwo people in the oral semaglutide 7 mg group died during the study. The abstract does not link the deaths to the drug.
Peptide
Semaglutide
Outcome
Not applicableDeaths, semaglutide 7 mg
Study
n = 426
Outcome group
Mortality · Whole body
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
deaths
2 deaths
semaglutide 7 mg
Source sentences
Summary
Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502913
13HumanRandomized controlled trialSafety outcome
Gastrointestinal events were the most frequent adverse events with oral semaglutide 14 mg: 193 of 425 participants (45%), most mild to moderate.
In plain wordsAbout 45% of people on oral semaglutide 14 mg had stomach or gut side effects, most of them mild to moderate.
Peptide
Semaglutide
Outcome
Not applicableGastrointestinal adverse events, semaglutide 14 mg
Study
n = 425
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
participants with gastrointestinal events
193 participants
semaglutide 14 mg
proportion
45%
semaglutide 14 mg
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502908
14HumanRandomized controlled trialSafety outcome
Fewer participants discontinued treatment due to adverse events with oral semaglutide 14 mg (21, 5%) than with orforglipron.
In plain wordsFewer people stopped oral semaglutide 14 mg because of side effects (5%) than stopped orforglipron.
Peptide
Semaglutide
Outcome
DecreaseDiscontinuation due to adverse events, semaglutide 14 mg
Study
n = 425
Comparator
Orforglipron
Outcome group
Adverse events · Whole body
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
discontinuations
21 participants
semaglutide 14 mg
proportion
5%
semaglutide 14 mg
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg)
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502910
15HumanRandomized controlled trialSafety outcome
Mean pulse rate increased by 1·5 bpm with oral semaglutide 14 mg, less than with orforglipron.
In plain wordsPulse rate rose by 1·5 beats per minute on oral semaglutide 14 mg, a smaller rise than with orforglipron.
Peptide
Semaglutide
Outcome
IncreasePulse rate increase, semaglutide 14 mg
Study
n = 425
Comparator
Orforglipron
Outcome group
Adverse events · Cardiovascular
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
mean pulse rate increase
1.5 bpm
semaglutide 14 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502912
16HumanRandomized controlled trialSafety outcome
In adults with diabetes, one death occurred in the orforglipron 12 mg group.
In plain wordsIn adults with diabetes, one death occurred in the orforglipron 12 mg group.
Peptide
Orforglipron
Outcome
Not applicableDeaths
Study
n = 424
Outcome group
Mortality · Whole body
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Deaths
1 deaths
orforglipron 12 mg
Source sentences
Summary
Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502932
17HumanRandomized controlled trialSafety outcome
In adults with diabetes, one death occurred in the orforglipron 36 mg group.
In plain wordsIn adults with diabetes, one death occurred in the orforglipron 36 mg group.
Peptide
Orforglipron
Outcome
Not applicableDeaths
Study
n = 423
Outcome group
Mortality · Whole body
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Deaths
1 deaths
orforglipron 36 mg
Source sentences
Summary
Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502933
18HumanRandomized controlled trialEfficacy outcome
HbA1c reduction at week 52 was smaller with oral semaglutide 14 mg than with orforglipron 12 mg (treatment difference -0·24% for orforglipron versus semaglutide).
In plain wordsOrforglipron 12 mg lowered HbA1c more than oral semaglutide 14 mg over 52 weeks in adults with type 2 diabetes.
Peptide
Semaglutide
Outcome
IncreaseHbA1c change versus orforglipron 12 mg, semaglutide 14 mg
Study
n: not reported in source
Comparator
Orforglipron 12 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
14 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
treatment difference (orforglipron 12 mg minus semaglutide 14 mg)
−0.24%
week 52
Source sentences
Summary
-0·24% (95% CI -0·41 to -0·072; p=0·0050) for orforglipron 12 mg versus semaglutide 14 mg
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502905
19HumanRandomized controlled trialEfficacy outcome
HbA1c reduction at week 52 was smaller with oral semaglutide 7 mg than with orforglipron 36 mg (treatment difference -0·68% for orforglipron versus semaglutide).
In plain wordsOrforglipron 36 mg lowered HbA1c more than oral semaglutide 7 mg over 52 weeks in adults with type 2 diabetes.
Peptide
Semaglutide
Outcome
IncreaseHbA1c change versus orforglipron 36 mg, semaglutide 7 mg
Study
n: not reported in source
Comparator
Orforglipron 36 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
7 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
treatment difference (orforglipron 36 mg minus semaglutide 7 mg)
−0.68%
week 52
Source sentences
Summary
-0·68% (-0·85 to -0·50; p<0·0001) for orforglipron 36 mg versus semaglutide 7 mg
1 context sentence(design, population, supporting numbers)
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502906
20HumanRandomized controlled trialEfficacy outcome
In adults with diabetes, orforglipron 12 mg reduced HbA1c more than semaglutide 14 mg, with a difference of -0·24%.
In plain wordsIn adults with diabetes, orforglipron 12 mg reduced HbA1c more than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
DecreaseHbA1c treatment difference
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c estimated treatment difference
−0.24%
orforglipron 12 mg versus semaglutide 14 mg
95% CI
−0.41 to −0.072%
orforglipron 12 mg versus semaglutide 14 mg
p-value
0.005
orforglipron 12 mg versus semaglutide 14 mg
Source sentences
Summary
-0·24% (95% CI -0·41 to -0·072; p=0·0050) for orforglipron 12 mg versus semaglutide 14 mg;
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502918
21HumanRandomized controlled trialEfficacy outcome
In adults with diabetes, orforglipron 36 mg reduced HbA1c more than semaglutide 7 mg, with a difference of -0·68%.
In plain wordsIn adults with diabetes, orforglipron 36 mg reduced HbA1c more than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
DecreaseHbA1c treatment difference
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
HbA1c estimated treatment difference
−0.68%
orforglipron 36 mg versus semaglutide 7 mg
CI
−0.85 to −0.5%
orforglipron 36 mg versus semaglutide 7 mg
p-value
< 0.0001
orforglipron 36 mg versus semaglutide 7 mg
Source sentences
Summary
-0·68% (-0·85 to -0·50; p<0·0001) for orforglipron 36 mg versus semaglutide 7 mg.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502919
22HumanRandomized controlled trialSafety outcome
In adults with diabetes, gastrointestinal events affected 59% on orforglipron 12 mg versus 37% on semaglutide 7 mg.
In plain wordsIn adults with diabetes, gastrointestinal events were more frequent with orforglipron 12 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal events
59%
orforglipron 12 mg (249 of 424)
Participants with gastrointestinal events
37%
semaglutide 7 mg (157 of 426)
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502920
23HumanRandomized controlled trialSafety outcome
In adults with diabetes, gastrointestinal events affected 59% on orforglipron 12 mg versus 45% on semaglutide 14 mg.
In plain wordsIn adults with diabetes, gastrointestinal events were more frequent with orforglipron 12 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal events
59%
orforglipron 12 mg (249 of 424)
Participants with gastrointestinal events
45%
semaglutide 14 mg (193 of 425)
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502921
24HumanRandomized controlled trialSafety outcome
In adults with diabetes, gastrointestinal events affected 58% on orforglipron 36 mg versus 37% on semaglutide 7 mg.
In plain wordsIn adults with diabetes, gastrointestinal events were more frequent with orforglipron 36 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal events
58%
orforglipron 36 mg (245 of 423)
Participants with gastrointestinal events
37%
semaglutide 7 mg (157 of 426)
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502922
25HumanRandomized controlled trialSafety outcome
In adults with diabetes, gastrointestinal events affected 58% on orforglipron 36 mg versus 45% on semaglutide 14 mg.
In plain wordsIn adults with diabetes, gastrointestinal events were more frequent with orforglipron 36 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants with gastrointestinal events
58%
orforglipron 36 mg (245 of 423)
Participants with gastrointestinal events
45%
semaglutide 14 mg (193 of 425)
Source sentences
Summary
The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity.
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502923
26HumanRandomized controlled trialSafety outcome
In adults with diabetes, adverse-event discontinuations affected 9% on orforglipron 12 mg versus 4% on semaglutide 7 mg.
In plain wordsIn adults with diabetes, adverse-event discontinuations were higher with orforglipron 12 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuation due to adverse events
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Adverse events · Whole body
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants who discontinued treatment due to adverse events
9%
orforglipron 12 mg (37 participants)
Participants who discontinued treatment due to adverse events
4%
semaglutide 7 mg (19 participants)
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg),
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502924
27HumanRandomized controlled trialSafety outcome
In adults with diabetes, adverse-event discontinuations affected 9% on orforglipron 12 mg versus 5% on semaglutide 14 mg.
In plain wordsIn adults with diabetes, adverse-event discontinuations were higher with orforglipron 12 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuation due to adverse events
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Adverse events · Whole body
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants who discontinued treatment due to adverse events
9%
orforglipron 12 mg (37 participants)
Participants who discontinued treatment due to adverse events
5%
semaglutide 14 mg (21 participants)
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg),
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502925
28HumanRandomized controlled trialSafety outcome
In adults with diabetes, adverse-event discontinuations affected 10% on orforglipron 36 mg versus 4% on semaglutide 7 mg.
In plain wordsIn adults with diabetes, adverse-event discontinuations were higher with orforglipron 36 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuation due to adverse events
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Adverse events · Whole body
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants who discontinued treatment due to adverse events
10%
orforglipron 36 mg (41 participants)
Participants who discontinued treatment due to adverse events
4%
semaglutide 7 mg (19 participants)
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg),
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502926
29HumanRandomized controlled trialSafety outcome
In adults with diabetes, adverse-event discontinuations affected 10% on orforglipron 36 mg versus 5% on semaglutide 14 mg.
In plain wordsIn adults with diabetes, adverse-event discontinuations were higher with orforglipron 36 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreaseDiscontinuation due to adverse events
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Adverse events · Whole body
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Participants who discontinued treatment due to adverse events
10%
orforglipron 36 mg (41 participants)
Participants who discontinued treatment due to adverse events
5%
semaglutide 14 mg (21 participants)
Source sentences
Summary
More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg),
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502927
30HumanRandomized controlled trialSafety outcome
In adults with diabetes, pulse increased by 3·7 bpm with orforglipron 12 mg versus 1·0 bpm with semaglutide 7 mg.
In plain wordsIn adults with diabetes, pulse increased more with orforglipron 12 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreasePulse rate increase
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Heart function · Cardiovascular
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean increase in pulse rate
3.7 bpm
orforglipron 12 mg
Mean increase in pulse rate
1 bpm
semaglutide 7 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502928
31HumanRandomized controlled trialSafety outcome
In adults with diabetes, pulse increased by 3·7 bpm with orforglipron 12 mg versus 1·5 bpm with semaglutide 14 mg.
In plain wordsIn adults with diabetes, pulse increased more with orforglipron 12 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreasePulse rate increase
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Heart function · Cardiovascular
Studied dose
12 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean increase in pulse rate
3.7 bpm
orforglipron 12 mg
Mean increase in pulse rate
1.5 bpm
semaglutide 14 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502929
32HumanRandomized controlled trialSafety outcome
In adults with diabetes, pulse increased by 4·7 bpm with orforglipron 36 mg versus 1·0 bpm with semaglutide 7 mg.
In plain wordsIn adults with diabetes, pulse increased more with orforglipron 36 mg than semaglutide 7 mg.
Peptide
Orforglipron
Outcome
IncreasePulse rate increase
Study
n: not reported in source
Comparator
Semaglutide 7 mg
Outcome group
Heart function · Cardiovascular
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean increase in pulse rate
4.7 bpm
orforglipron 36 mg
Mean increase in pulse rate
1 bpm
semaglutide 7 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502930
33HumanRandomized controlled trialSafety outcome
In adults with diabetes, pulse increased by 4·7 bpm with orforglipron 36 mg versus 1·5 bpm with semaglutide 14 mg.
In plain wordsIn adults with diabetes, pulse increased more with orforglipron 36 mg than semaglutide 14 mg.
Peptide
Orforglipron
Outcome
IncreasePulse rate increase
Study
n: not reported in source
Comparator
Semaglutide 14 mg
Outcome group
Heart function · Cardiovascular
Studied dose
36 mg · oral · 52 weeksAs given in this study (human).
Measurements
Mean increase in pulse rate
4.7 bpm
orforglipron 36 mg
Mean increase in pulse rate
1.5 bpm
semaglutide 14 mg
Source sentences
Summary
mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm).
2 context sentences(design, population, supporting numbers)
Summary · context
This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
Summary · context
Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day.
Report a problemFND-4176502931

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 postedNCT06045221

A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin

Eli Lilly and Companyn = 1,69822 Sept 2023 to 22 Aug 2025

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 15 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.

Versions 4 to 15Current
28 Oct 2026, 02:03 UTC
The same notice was added 12 times, first on 14 Oct 2026, 05:02 UTC. The status did not change between them.
Study results updated
Version 3
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Version 2
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC