Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation.

Xu Y, Huang T, Zhang Y, Ji D, Tuttle KR, Carrero JJ, Fu EL

Circulation24 Feb 2026

PMID41732861DOI10.1161/circulationaha.125.075157PepBankPUB-41732861

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 study8

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone8

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

01HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including liraglutide were associated with lower 3-year heart-failure-hospitalization risk than DPP-4 inhibitors (3.4% versus 4.3%; weighted HR 0.77, 95% CI 0.66-0.91).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including liraglutide were linked to fewer heart-failure hospitalizations than DPP-4 inhibitors.
Peptide
Liraglutide
Outcome
DecreaseHeart failure hospitalization at 3 years
Study
n = 32,979
Comparator
DPP-4 inhibitor
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
0.77
pooled GLP-1 receptor agonists versus DPP-4 inhibitors
Absolute risk
3.4%
pooled GLP-1 receptor agonists; 3 years
Absolute risk
4.3%
DPP-4 inhibitors; 3 years
Source sentences
Summary
Starting a GLP-1RA was associated with a lower 3-year absolute risk of HHF than starting a DPP-4i (3.4% versus 4.3%), corresponding to a weighted hazard ratio of 0.77 (95% CI, 0.66-0.91).
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4173286101
02HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including semaglutide were associated with lower 3-year heart-failure-hospitalization risk than DPP-4 inhibitors (3.4% versus 4.3%; weighted HR 0.77, 95% CI 0.66-0.91).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including semaglutide were linked to fewer heart-failure hospitalizations than DPP-4 inhibitors.
Peptide
Semaglutide
Outcome
DecreaseHeart failure hospitalization at 3 years
Study
n = 32,979
Comparator
DPP-4 inhibitor
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
0.77
pooled GLP-1 receptor agonists versus DPP-4 inhibitors
Absolute risk
3.4%
pooled GLP-1 receptor agonists; 3 years
Absolute risk
4.3%
DPP-4 inhibitors; 3 years
Source sentences
Summary
Starting a GLP-1RA was associated with a lower 3-year absolute risk of HHF than starting a DPP-4i (3.4% versus 4.3%), corresponding to a weighted hazard ratio of 0.77 (95% CI, 0.66-0.91).
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4173286102
03HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including liraglutide had 3-year heart-failure-hospitalization risks of 3.6% versus 3.3% with SGLT-2 inhibitors (weighted HR 1.02, 95% CI 0.85-1.18).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including liraglutide had an uncertain heart-failure-hospitalization comparison with SGLT-2 inhibitors.
Peptide
Liraglutide
Outcome
No significant changeHeart failure hospitalization at 3 years
Study
n = 30,104
Comparator
SGLT-2 inhibitor
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
1.02
pooled GLP-1 receptor agonists versus SGLT-2 inhibitors
Absolute risk
3.6%
pooled GLP-1 receptor agonists; 3 years
Absolute risk
3.3%
SGLT-2 inhibitors; 3 years
Source sentences
Summary
Absolute 3-year risks for GLP-1RA compared with SGLT-2i on HHF were 3.6% and 3.3% with a weighted hazard ratio of 1.02 (95% CI, 0.85-1.18).
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4173286103
04HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including semaglutide had 3-year heart-failure-hospitalization risks of 3.6% versus 3.3% with SGLT-2 inhibitors (weighted HR 1.02, 95% CI 0.85-1.18).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including semaglutide had an uncertain heart-failure-hospitalization comparison with SGLT-2 inhibitors.
Peptide
Semaglutide
Outcome
No significant changeHeart failure hospitalization at 3 years
Study
n = 30,104
Comparator
SGLT-2 inhibitor
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
1.02
pooled GLP-1 receptor agonists versus SGLT-2 inhibitors
Absolute risk
3.6%
pooled GLP-1 receptor agonists; 3 years
Absolute risk
3.3%
SGLT-2 inhibitors; 3 years
Source sentences
Summary
Absolute 3-year risks for GLP-1RA compared with SGLT-2i on HHF were 3.6% and 3.3% with a weighted hazard ratio of 1.02 (95% CI, 0.85-1.18).
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4173286104
05HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including liraglutide were associated with a lower major-adverse-cardiovascular-event rate than DPP-4 inhibitors (weighted HR 0.85, 95% CI 0.74-0.99).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including liraglutide were linked to fewer major cardiovascular events than DPP-4 inhibitors.
Peptide
Liraglutide
Outcome
DecreaseMajor adverse cardiovascular events
Study
n = 32,979
Comparator
DPP-4 inhibitor
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
0.85
pooled GLP-1 receptor agonists versus DPP-4 inhibitors
Source sentences
Summary
In positive control outcome analyses, GLP-1RA use was associated with a lower rate of major adverse cardiovascular events than DPP-4i use (weighted hazard ratio, 0.85 [95% CI, 0.74-0.99]), consistent with trial findings.
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4173286105
06HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including semaglutide were associated with a lower major-adverse-cardiovascular-event rate than DPP-4 inhibitors (weighted HR 0.85, 95% CI 0.74-0.99).
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs including semaglutide were linked to fewer major cardiovascular events than DPP-4 inhibitors.
Peptide
Semaglutide
Outcome
DecreaseMajor adverse cardiovascular events
Study
n = 32,979
Comparator
DPP-4 inhibitor
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Weighted hazard ratio
0.85
pooled GLP-1 receptor agonists versus DPP-4 inhibitors
Source sentences
Summary
In positive control outcome analyses, GLP-1RA use was associated with a lower rate of major adverse cardiovascular events than DPP-4i use (weighted hazard ratio, 0.85 [95% CI, 0.74-0.99]), consistent with trial findings.
3 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
Summary · context
Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4173286106
07HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including liraglutide had the largest absolute heart-failure-hospitalization risk difference among patients with higher predicted baseline heart-failure risk.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs showed the largest heart-failure risk difference in people with higher predicted baseline risk.
Peptide
Liraglutide
Outcome
Direction not reportedHeart failure hospitalization risk difference by predicted baseline risk
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
The absolute risk difference was largest for patients with higher predicted risk of heart failure at baseline.
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4173286107
08HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists including semaglutide had the largest absolute heart-failure-hospitalization risk difference among patients with higher predicted baseline heart-failure risk.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs showed the largest heart-failure risk difference in people with higher predicted baseline risk.
Peptide
Semaglutide
Outcome
Direction not reportedHeart failure hospitalization risk difference by predicted baseline risk
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
The absolute risk difference was largest for patients with higher predicted risk of heart failure at baseline.
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i.
Summary · context
Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4173286108

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

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
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Subjects

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