Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus.

Bu F, Wu R, Ostropolets A, Aminorroaya A, Chen HY, Chai Y, Dhingra LS, Falconer T, Hsu JC, Kim C, Lau WCY, Man KKC and 9 more

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Minty E, Morales DR, Nishimura A, Thangraraj P, Van Zandt M, Yin C, Khera R, Hripcsak G, Suchard MA

Journal of the American College of Cardiology15 Apr 2026Cited by 1 (Europe PMC)

PMID41984016PMCIDPMC13191718DOI10.1016/j.jacc.2026.02.5123PepBankPUB-41984016

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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: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study7

4 results from studies that gave the peptide. 4 results from people.

01HumanObservational studyEfficacy outcome
In adults with T2D receiving metformin, semaglutide versus empagliflozin had an estimated 3-point MACE HR of 1.05 (95% CI 0.79-1.39), with uncertainty including no difference.
In plain wordsIn adults with type 2 diabetes receiving metformin, semaglutide showed no clear 3-point heart-event risk difference versus empagliflozin.
Peptide
Semaglutide
Outcome
No significant change3-point major adverse cardiovascular events
Study
n: not reported in source
Comparator
Empagliflozin
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Hazard ratio
1.05
semaglutide versus empagliflozin; 3-point MACE; 95% CI 0.79-1.39
Source sentences
Summary
For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup.
4 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
Report a problemFND-4198401602
02HumanObservational studyEfficacy outcome
In adults with T2D receiving metformin, semaglutide versus empagliflozin had an estimated 4-point MACE HR of 0.95 (95% CI 0.81-1.12), with uncertainty including no difference.
In plain wordsIn adults with type 2 diabetes receiving metformin, semaglutide showed no clear 4-point heart-event risk difference versus empagliflozin.
Peptide
Semaglutide
Outcome
No significant change4-point major adverse cardiovascular events
Study
n: not reported in source
Comparator
Empagliflozin
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Hazard ratio
0.95
semaglutide versus empagliflozin; 4-point MACE; 95% CI 0.81-1.12
Source sentences
Summary
For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup.
4 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
Report a problemFND-4198401603
03HumanObservational studyEfficacy outcome
In adults with T2D receiving metformin and established CVD, semaglutide versus empagliflozin 3-point MACE findings were reported as consistent with the overall cohort.
In plain wordsIn adults with type 2 diabetes and cardiovascular disease, semaglutide-versus-empagliflozin 3-point heart-event findings were consistent with the overall cohort.
Peptide
Semaglutide
Outcome
Not applicable3-point major adverse cardiovascular events in established cardiovascular disease
Study
n: not reported in source
Comparator
Empagliflozin
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup.
5 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
A secondary subgroup analysis included 316,242 patients with established cardiovascular diseases (CVDs).
Summary · context
Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
Report a problemFND-4198401604
04HumanObservational studyEfficacy outcome
In adults with T2D receiving metformin and established CVD, semaglutide versus empagliflozin 4-point MACE findings were reported as consistent with the overall cohort.
In plain wordsIn adults with type 2 diabetes and cardiovascular disease, semaglutide-versus-empagliflozin 4-point heart-event findings were consistent with the overall cohort.
Peptide
Semaglutide
Outcome
Not applicable4-point major adverse cardiovascular events in established cardiovascular disease
Study
n: not reported in source
Comparator
Empagliflozin
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup.
5 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
A secondary subgroup analysis included 316,242 patients with established cardiovascular diseases (CVDs).
Summary · context
Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
Report a problemFND-4198401605

Studies that did not test the peptide alone3

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.

05HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In adults with type 2 diabetes, individual GLP-1 receptor agonists and SGLT2 inhibitors showed broadly similar cardiovascular effectiveness within and across classes.
In plain wordsIn adults with diabetes, individual drugs in both classes, including dulaglutide, were linked to broadly similar cardiovascular effectiveness.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeCardiovascular effectiveness
Study
n = 1,245,211
Comparator
Other individual GLP-1 receptor agonists and SGLT2 inhibitors
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Across the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes.
3 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy
Summary · context
with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Report a problemFND-4198401607
06HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In adults with T2D receiving metformin, the cohort reported broadly similar cardiovascular effectiveness within and across GLP-1 receptor agonist and SGLT2 inhibitor classes.
In plain wordsIn adults with type 2 diabetes receiving metformin, GLP-1 and SGLT2 drugs had broadly similar cardiovascular effectiveness within and across classes.
Peptide
Liraglutide
Outcome
Not applicableCardiovascular effectiveness
Study
n: not reported in source
Comparator
GLP-1 receptor agonists and SGLT2 inhibitors within and across classes
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Across the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes.
3 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
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-4198401601
07HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In adults with T2D receiving metformin, the cohort reported broadly similar cardiovascular effectiveness within and across GLP-1 receptor agonist and SGLT2 inhibitor classes.
In plain wordsIn adults with type 2 diabetes receiving metformin, GLP-1 and SGLT2 drugs had broadly similar cardiovascular effectiveness within and across classes.
Peptide
Semaglutide
Outcome
Not applicableCardiovascular effectiveness across drug classes
Study
n: not reported in source
Comparator
GLP-1 receptor agonists and SGLT2 inhibitors within and across classes
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Across the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes.
3 context sentences(design, population, supporting numbers)
Summary · context
We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases.
Summary · context
The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin).
Summary · context
HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding.
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-4198401606

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.

Versions 8 to 11Current
28 Oct 2026, 02:03 UTC
The same notice was added 4 times, first on 27 Oct 2026, 18:20 UTC. The status did not change between them.
Study results updated
Version 7
27 Oct 2026, 16:36 UTC
Study data updated · source update from Europe PMC
Versions 5 to 6
22 Oct 2026, 02:26 UTC
The same notice was added 2 times, first on 22 Oct 2026, 02:26 UTC. The status did not change between them.
Study results updated
Version 4
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 3
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

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Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus.

Summary

Results from this study7

Studies that did not test the peptide alone3

Version history

Subjects

Publication types

MeSH terms

Keywords