GLP-1-based therapies and limb outcomes in PAD: a systematic review and meta-analysis of real-world studies.

Boccatonda A, D'Ardes D, Brighenti A, Cipollone A, Simeone PG, Guagnano MT, Serra C, Santilli F, Cipollone F

Diabetes research and clinical practice19 Apr 2026

PMID42009258DOI10.1016/j.diabres.2026.113271PepBankPUB-42009258

Publisher page PubMedAsk about this study

Summary

AimsGlucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual incretin agonist tirzepatide have demonstrated cardiometabolic benefits in cardiovascular outcome trials, but their effects on limb outcomes in peripheral artery disease (PAD) remain unclear. This study evaluated whether GLP-1-based therapies reduce the risk of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality in real-world PAD populations.MethodsA systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.ResultsSix studies including over 240,000 patients were analyzed. GLP-1-based therapies were associated with a significant reduction in MALE (HR 0.59, 95% CI 0.39-0.90), although heterogeneity was substantial. A significant reduction in MACE was also observed (HR 0.67, 95% CI 0.53-0.85), with greater consistency in diabetic populations. Stroke was significantly reduced (HR 0.75, 95% CI 0.63-0.89), demonstrating consistent effects across studies. Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude.ConclusionIn real-world PAD populations, GLP-1-based therapies are associated with meaningful reductions in both limb and cardiovascular outcomes. These findings support a vascular protective profile, particularly for stroke and MACE in more homogeneous populations such as patients with diabetes.

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

Results from this study5

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

Studies that did not test the peptide alone5

In this study, Tirzepatide 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 Tirzepatide.

01HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with peripheral artery disease, pooled GLP-1-based therapies (GLP-1 receptor agonists and tirzepatide) were associated with a significant reduction in major adverse limb events (HR 0.59, 95% CI 0.39-0.90).
In plain wordsIn adults with peripheral artery disease, GLP-1-based drugs taken together were linked to fewer major limb events in real-world studies.
Peptide
Tirzepatide
Outcome
DecreaseMajor adverse limb events (MALE)
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.59 ratio
MALE
Source sentences
Summary
GLP-1-based therapies were associated with a significant reduction in MALE (HR 0.59, 95% CI 0.39-0.90), although heterogeneity was substantial.
2 context sentences(design, population, supporting numbers)
Summary · context
A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.
Summary · context
Six studies including over 240,000 patients were analyzed.
In this study, Tirzepatide 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 Tirzepatide.
Show in the study text Report a problemFND-4200925801
02HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with peripheral artery disease, pooled GLP-1-based therapies were associated with a significant reduction in MACE (HR 0.67, 95% CI 0.53-0.85).
In plain wordsIn adults with peripheral artery disease, GLP-1-based drugs taken together were linked to fewer major cardiovascular events in real-world studies.
Peptide
Tirzepatide
Outcome
DecreaseMajor adverse cardiovascular events (MACE)
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.67 ratio
MACE
Source sentences
Summary
A significant reduction in MACE was also observed (HR 0.67, 95% CI 0.53-0.85), with greater consistency in diabetic populations.
2 context sentences(design, population, supporting numbers)
Summary · context
A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.
Summary · context
Six studies including over 240,000 patients were analyzed.
In this study, Tirzepatide 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 Tirzepatide.
Show in the study text Report a problemFND-4200925802
03HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with peripheral artery disease, pooled GLP-1-based therapies were associated with a significant reduction in stroke (HR 0.75, 95% CI 0.63-0.89).
In plain wordsIn adults with peripheral artery disease, GLP-1-based drugs taken together were linked to fewer strokes in real-world studies.
Peptide
Tirzepatide
Outcome
DecreaseStroke
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.75 ratio
stroke
Source sentences
Summary
Stroke was significantly reduced (HR 0.75, 95% CI 0.63-0.89), demonstrating consistent effects across studies.
2 context sentences(design, population, supporting numbers)
Summary · context
A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.
Summary · context
Six studies including over 240,000 patients were analyzed.
In this study, Tirzepatide 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 Tirzepatide.
Show in the study text Report a problemFND-4200925803
04HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with peripheral artery disease, pooled GLP-1-based therapies were associated with a significant reduction in myocardial infarction, with variable effect size.
In plain wordsIn adults with peripheral artery disease, GLP-1-based drugs taken together were linked to fewer heart attacks, with varying size of effect.
Peptide
Tirzepatide
Outcome
DecreaseMyocardial infarction
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude.
2 context sentences(design, population, supporting numbers)
Summary · context
A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.
Summary · context
Six studies including over 240,000 patients were analyzed.
In this study, Tirzepatide 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 Tirzepatide.
Show in the study text Report a problemFND-4200925804
05HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with peripheral artery disease, pooled GLP-1-based therapies were associated with a significant reduction in all-cause mortality, with variable effect size.
In plain wordsIn adults with peripheral artery disease, GLP-1-based drugs taken together were linked to fewer deaths, with varying size of effect.
Peptide
Tirzepatide
Outcome
DecreaseAll-cause mortality
Study
n: not reported in source
Outcome group
Mortality · Cardiovascular
Source sentences
Summary
Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude.
2 context sentences(design, population, supporting numbers)
Summary · context
A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD.
Summary · context
Six studies including over 240,000 patients were analyzed.
In this study, Tirzepatide 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 Tirzepatide.
Show in the study text Report a problemFND-4200925805

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 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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