Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.

Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP

The New England journal of medicine11 May 2025Cited by 420 (Europe PMC)

PMID40353578DOI10.1056/nejmoa2416394PepBankPUB-40353578

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 study14

14 results from studies that gave the peptide. 14 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, tirzepatide reduced body weight by 20.2% at week 72, more than semaglutide.
In plain wordsIn adults with obesity and no diabetes, tirzepatide lowered body weight more than semaglutide after 72 weeks.
Peptide
Tirzepatide
Outcome
DecreasePercent change in body weight at week 72
Study
n = 751
Comparator
Semaglutide
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Measurements
Weight change
−20.2%
tirzepatide
Source sentences
Summary
The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357801
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, semaglutide reduced body weight by 13.7% at week 72, less than tirzepatide.
In plain wordsIn adults with obesity and no diabetes, semaglutide lowered body weight, but less than tirzepatide did, after 72 weeks.
Peptide
Semaglutide
Outcome
DecreasePercent change in body weight at week 72
Study
n = 751
Comparator
Tirzepatide
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Measurements
Weight change
−13.7%
semaglutide
Source sentences
Summary
The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357802
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, tirzepatide reduced waist circumference by 18.4 cm at week 72, more than semaglutide.
In plain wordsIn adults with obesity and no diabetes, tirzepatide shrank waist size more than semaglutide after 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseChange in waist circumference at week 72
Study
n = 751
Comparator
Semaglutide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Measurements
Waist circumference change
−18.4 cm
tirzepatide
Source sentences
Summary
The least-squares mean change in waist circumference was -18.4 cm (95% CI, -19.6 to -17.2) with tirzepatide and -13.0 cm (95% CI, -14.3 to -11.7) with semaglutide (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357803
04HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, semaglutide reduced waist circumference by 13.0 cm at week 72, less than tirzepatide.
In plain wordsIn adults with obesity and no diabetes, semaglutide shrank waist size, but less than tirzepatide did, after 72 weeks.
Peptide
Semaglutide
Outcome
DecreaseChange in waist circumference at week 72
Study
n = 751
Comparator
Tirzepatide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Measurements
Waist circumference change
−13 cm
semaglutide
Source sentences
Summary
The least-squares mean change in waist circumference was -18.4 cm (95% CI, -19.6 to -17.2) with tirzepatide and -13.0 cm (95% CI, -14.3 to -11.7) with semaglutide (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357804
05HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, more participants on tirzepatide than on semaglutide had a weight reduction of at least 10%.
In plain wordsIn adults with obesity and no diabetes, more people on tirzepatide than on semaglutide lost at least 10% of body weight.
Peptide
Tirzepatide
Outcome
IncreaseWeight reduction of at least 10%
Study
n = 751
Comparator
Semaglutide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357805
06HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, more participants on tirzepatide than on semaglutide had a weight reduction of at least 15%.
In plain wordsIn adults with obesity and no diabetes, more people on tirzepatide than on semaglutide lost at least 15% of body weight.
Peptide
Tirzepatide
Outcome
IncreaseWeight reduction of at least 15%
Study
n = 751
Comparator
Semaglutide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357806
07HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, more participants on tirzepatide than on semaglutide had a weight reduction of at least 20%.
In plain wordsIn adults with obesity and no diabetes, more people on tirzepatide than on semaglutide lost at least 20% of body weight.
Peptide
Tirzepatide
Outcome
IncreaseWeight reduction of at least 20%
Study
n = 751
Comparator
Semaglutide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357807
08HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, more participants on tirzepatide than on semaglutide had a weight reduction of at least 25%.
In plain wordsIn adults with obesity and no diabetes, more people on tirzepatide than on semaglutide lost at least 25% of body weight.
Peptide
Tirzepatide
Outcome
IncreaseWeight reduction of at least 25%
Study
n = 751
Comparator
Semaglutide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357808
09HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, fewer participants on semaglutide than on tirzepatide had a weight reduction of at least 10%.
In plain wordsIn adults with obesity and no diabetes, fewer people on semaglutide than on tirzepatide lost at least 10% of body weight.
Peptide
Semaglutide
Outcome
DecreaseWeight reduction of at least 10%
Study
n = 751
Comparator
Tirzepatide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357809
10HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, fewer participants on semaglutide than on tirzepatide had a weight reduction of at least 15%.
In plain wordsIn adults with obesity and no diabetes, fewer people on semaglutide than on tirzepatide lost at least 15% of body weight.
Peptide
Semaglutide
Outcome
DecreaseWeight reduction of at least 15%
Study
n = 751
Comparator
Tirzepatide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357810
11HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, fewer participants on semaglutide than on tirzepatide had a weight reduction of at least 20%.
In plain wordsIn adults with obesity and no diabetes, fewer people on semaglutide than on tirzepatide lost at least 20% of body weight.
Peptide
Semaglutide
Outcome
DecreaseWeight reduction of at least 20%
Study
n = 751
Comparator
Tirzepatide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357811
12HumanRandomized controlled trialEfficacy outcome
In adults with obesity but without type 2 diabetes, fewer participants on semaglutide than on tirzepatide had a weight reduction of at least 25%.
In plain wordsIn adults with obesity and no diabetes, fewer people on semaglutide than on tirzepatide lost at least 25% of body weight.
Peptide
Semaglutide
Outcome
DecreaseWeight reduction of at least 25%
Study
n = 751
Comparator
Tirzepatide
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357812
13HumanRandomized controlled trialSafety outcome
In adults with obesity but without type 2 diabetes, the most common adverse events with tirzepatide were gastrointestinal, mostly mild to moderate and during dose escalation.
In plain wordsIn adults with obesity and no diabetes, the most common side effects of tirzepatide were stomach and bowel problems, mostly mild to moderate.
Peptide
Tirzepatide
Outcome
Not applicableAdverse events (gastrointestinal)
Study
n = 751
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
maximum tolerated dose (10 mg or 15 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357813
14HumanRandomized controlled trialSafety outcome
In adults with obesity but without type 2 diabetes, the most common adverse events with semaglutide were gastrointestinal, mostly mild to moderate and during dose escalation.
In plain wordsIn adults with obesity and no diabetes, the most common side effects of semaglutide were stomach and bowel problems, mostly mild to moderate.
Peptide
Semaglutide
Outcome
Not applicableAdverse events (gastrointestinal)
Study
n = 751
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
maximum tolerated dose (1.7 mg or 2.4 mg) · subcutaneous · 72 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks.
Report a problemFND-4035357814

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 postedNCT05822830

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities

Eli Lilly and Companyn = 75121 Apr 2023 to 13 Nov 2024

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 26 Nov 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 3Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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