Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study.

Qadeer A, Khalid MB, Syed R, Jain S, Zakaria F, Khan MHA, Gohar N, Shoukat A, Mortada I, Hamza I, Motiwala A, Raja MW, Blackwell T, Jneid H

Diabetes & vascular disease research1 May 2026

PMID42376874PMCIDPMC13319829DOI10.1177/14791641261465360PepBankPUB-42376874

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Summary

BackgroundWith the increasing use of GLP-1 receptor agonists and dual GIP/GLP-1 agonists for managing obesity and type 2 diabetes, understanding their real-world effectiveness and safety is essential. This TriNetX analysis directly compares clinical outcomes among patients treated with tirzepatide vs semaglutide.MethodWe utilized data from the TriNetX Research Network, identifying patients aged > 40 years or with obesity ("BMI ≥ 30 kg/m2") and type 2 diabetes (HbA1c ≥ 6.5% or fasting glucose.≥ 125 mg/dL). Qualifying events were restricted to May 1, 2022, through November 21, 2024. We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists. The index date was defined as the first co-occurrence of the obesity/diabetes criteria and the respective drug prescription. To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort. Outcomes, including all-cause mortality, MACE, heart failure exacerbation, ischemic stroke/TIA, hospitalization/ED use, dementia, UTI, adverse Gastrointestinal (GI) effects, and changes in HbA1c, were assessed within a 1-year window after the index date.ResultsOur matched cohort had a mean age of 75 years, with 45% male patients and 74% identified as white. Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978). All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562). The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up. There was no significant difference in heart failure exacerbation or UTI incidence. GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997), while hospitalization or emergency visits were comparable between the two groups.ConclusionIn this propensity matched cohort of patients with obesity and type 2 diabetes, tirzepatide demonstrated improved cardiometabolic outcomes compared to semaglutide, including lower all-cause mortality and lower HbA1c. These findings support the cardiovascular safety and efficacy of tirzapetide and highlight the need for further studies to evaluate its effectiveness in broader clinical populations.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

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

01HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, tirzepatide had a significantly lower 1-year MACE incidence than semaglutide (3.7% vs 4.1%).
In plain wordsIn adults with obesity and type 2 diabetes, serious heart events were slightly less common with tirzepatide than with semaglutide.
Peptide
Tirzepatide
Outcome
DecreaseMACE
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
MACE incidence
3.7%
tirzepatide
MACE incidence
4.1%
semaglutide
Risk ratio
0.918 ratio
tirzepatide vs semaglutide
Source sentences
Summary
Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978).
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687401
02HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, semaglutide had a higher 1-year MACE incidence than tirzepatide (4.1% vs 3.7%).
In plain wordsIn adults with obesity and type 2 diabetes, serious heart events were slightly more common with semaglutide than with tirzepatide.
Peptide
Semaglutide
Outcome
IncreaseMACE
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
MACE incidence
4.1%
semaglutide
MACE incidence
3.7%
tirzepatide
Risk ratio
0.918 ratio
tirzepatide vs semaglutide
Source sentences
Summary
Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978).
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687402
03HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, all-cause mortality was lower with tirzepatide than with semaglutide (0.2% vs. 0.4%).
In plain wordsIn adults with obesity and type 2 diabetes, fewer deaths occurred with tirzepatide than with semaglutide.
Peptide
Tirzepatide
Outcome
DecreaseAll-cause mortality
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Measurements
All-cause mortality
0.2%
tirzepatide
All-cause mortality
0.4%
semaglutide
Risk ratio
0.436 ratio
tirzepatide vs semaglutide
Source sentences
Summary
All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562).
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687403
04HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, all-cause mortality was higher with semaglutide than with tirzepatide (0.4% vs. 0.2%).
In plain wordsIn adults with obesity and type 2 diabetes, more deaths occurred with semaglutide than with tirzepatide.
Peptide
Semaglutide
Outcome
IncreaseAll-cause mortality
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Measurements
All-cause mortality
0.4%
semaglutide
All-cause mortality
0.2%
tirzepatide
Risk ratio
0.436 ratio
tirzepatide vs semaglutide
Source sentences
Summary
All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562).
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687404
05HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, tirzepatide gave a lower mean HbA1c than semaglutide (6.565% vs. 6.848%).
In plain wordsIn adults with obesity and type 2 diabetes, blood sugar control (HbA1c) was better with tirzepatide than with semaglutide.
Peptide
Tirzepatide
Outcome
DecreaseMean HbA1c during follow-up
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
Mean HbA1c
6.565%
tirzepatide
Mean HbA1c
6.848%
semaglutide
Source sentences
Summary
The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up.
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687405
06HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, semaglutide gave a higher mean HbA1c than tirzepatide (6.848% vs. 6.565%).
In plain wordsIn adults with obesity and type 2 diabetes, blood sugar control (HbA1c) was less good with semaglutide than with tirzepatide.
Peptide
Semaglutide
Outcome
IncreaseMean HbA1c during follow-up
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
Mean HbA1c
6.848%
semaglutide
Mean HbA1c
6.565%
tirzepatide
Source sentences
Summary
The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up.
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687406
07HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, heart failure exacerbation did not differ significantly between tirzepatide and semaglutide.
In plain wordsIn adults with obesity and type 2 diabetes, heart failure flare-ups were not clearly different between tirzepatide and semaglutide.
Peptide
Tirzepatide
Outcome
No significant changeHeart failure exacerbation
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
There was no significant difference in heart failure exacerbation
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687407
08HumanObservational studyEfficacy outcome
In propensity-matched adults with obesity and type 2 diabetes, heart failure exacerbation did not differ significantly between semaglutide and tirzepatide.
In plain wordsIn adults with obesity and type 2 diabetes, heart failure flare-ups were not clearly different between semaglutide and tirzepatide.
Peptide
Semaglutide
Outcome
No significant changeHeart failure exacerbation
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
There was no significant difference in heart failure exacerbation
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687408
09HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, UTI incidence did not differ significantly between tirzepatide and semaglutide.
In plain wordsIn adults with obesity and type 2 diabetes, urinary infections were not clearly different between tirzepatide and semaglutide.
Peptide
Tirzepatide
Outcome
No significant changeUTI incidence
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Adverse events · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
There was no significant difference in heart failure exacerbation or UTI incidence.
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687409
10HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, UTI incidence did not differ significantly between semaglutide and tirzepatide.
In plain wordsIn adults with obesity and type 2 diabetes, urinary infections were not clearly different between semaglutide and tirzepatide.
Peptide
Semaglutide
Outcome
No significant changeUTI incidence
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Adverse events · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
There was no significant difference in heart failure exacerbation or UTI incidence.
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687410
11HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, GI side effects were slightly less frequent with tirzepatide than with semaglutide (9.8% vs. 10.2%).
In plain wordsIn adults with obesity and type 2 diabetes, stomach and gut side effects were slightly less common with tirzepatide than with semaglutide.
Peptide
Tirzepatide
Outcome
DecreaseGastrointestinal side effects
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
GI side effects
9.8%
tirzepatide
GI side effects
10.2%
semaglutide
Risk ratio
0.959 ratio
tirzepatide vs semaglutide
Source sentences
Summary
GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997)
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687411
12HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, GI side effects were slightly more frequent with semaglutide than with tirzepatide (10.2% vs. 9.8%).
In plain wordsIn adults with obesity and type 2 diabetes, stomach and gut side effects were slightly more common with semaglutide than with tirzepatide.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal side effects
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
GI side effects
10.2%
semaglutide
GI side effects
9.8%
tirzepatide
Risk ratio
0.959 ratio
tirzepatide vs semaglutide
Source sentences
Summary
GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997)
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687412
13HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, hospitalization or emergency visits were comparable between tirzepatide and semaglutide.
In plain wordsIn adults with obesity and type 2 diabetes, hospital and emergency visits were similar with tirzepatide and semaglutide.
Peptide
Tirzepatide
Outcome
No significant changeHospitalization or emergency visits
Study
n = 47,804
Comparator
Semaglutide
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
while hospitalization or emergency visits were comparable between the two groups
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687413
14HumanObservational studySafety outcome
In propensity-matched adults with obesity and type 2 diabetes, hospitalization or emergency visits were comparable between semaglutide and tirzepatide.
In plain wordsIn adults with obesity and type 2 diabetes, hospital and emergency visits were similar with semaglutide and tirzepatide.
Peptide
Semaglutide
Outcome
No significant changeHospitalization or emergency visits
Study
n = 47,804
Comparator
Tirzepatide
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
while hospitalization or emergency visits were comparable between the two groups
2 context sentences(design, population, supporting numbers)
Summary · context
We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists.
Summary · context
To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort.
Show in the study text Report a problemFND-4237687414

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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

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Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study.

Summary

Results from this study14

Version history

Subjects

Publication types

MeSH terms

Keywords