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Purpose of Review <p>Peripheral artery disease (PAD) is a serious complication in type 2 diabetes, increasing vascular morbidity and mortality. While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists show cardiovascular benefits in diabetes, their effects on PAD-related outcomes are unclear. This meta-analysis assessed the impact of these therapies on vascular outcomes in type 2 diabetes with PAD.</p> Recent Findings <p>A systematic review and meta-analysis were conducted per PRISMA guidelines (PROSPERO CRD420251083622). PubMed, Embase, and Cochrane Central were searched. A random-effects model pooled data. Primary outcomes were major adverse limb events, peripheral revascularization, and amputation. Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction, stroke, HbA1c, and weight changes. Six studies (four RCTs, two propensity score-matched cohorts) with 25,866 patients were included. Incretin-based therapies significantly reduced all-cause mortality (RR 0.52 [0.28–0.95], <i>p</i> = 0.032) and HbA1c (MD − 0.73% [–1.32 to − 0.15], <i>p</i> = 0.013) compared to placebo or standard care. No significant differences were found for major adverse limb events, revascularization, amputation, MACE, myocardial infarction, or stroke. Heterogeneity and low evidence certainty were noted.</p> Graphical Abstract <p>Summary of a systematic review and meta-analysis evaluating glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptoragonists in patients with type 2 diabetes mellitus (T2DM) and peripheralartery disease (PAD). Outcomes included mortality, major adverse limb events, peripheral revascularization, amputation, myocardial infarction(MI), major adverse cardiovascular events (MACE), stroke, and glycemic control. Results demonstrated reduced mortality and improved glycemiccontrol with incretin-based therapy, while limb-related outcomes andcardiovascular endpoints showed no statistically significant differences.GLP-1 = glucagon-like peptide-1; GIP = glucose-dependent insulinotropicpolypeptide; T2DM = type 2 diabetes mellitus; PAD = peripheral arterydisease; RCTs = randomized controlled trials; PSM = propensity-scorematched studies; RR = risk ratio; HR = hazard ratio; MD = meandifference; CI = confidence interval; I² = heterogeneity index; MACE =major adverse cardiovascular events; MI = myocardial infarction; HbA1c= glycated hemoglobin. Illustration created with Biorender</p> <p></p>

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Glucagon-Like Peptide-1 and Dual Incretin Agonists in Type 2 Diabetes with Peripheral Artery Disease: A Systematic Review and Meta-Analysis of Vascular, Cardiovascular, Metabolic, and Mortality Outcomes

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Larissa Araújo de Lucena,
  • Deivyd V. S. Cavalcante,
  • Marcela V. Montenegro,
  • Larissa C. Hespanhol,
  • William S. de Oliveira,
  • Juliana Q. Muniz,
  • Sruti Prathivadhi-Bhayankaram,
  • Edgardo Kaplinsky,
  • Alejandro Barbagelata,
  • Juliana Giorgi

摘要

Purpose of Review

Peripheral artery disease (PAD) is a serious complication in type 2 diabetes, increasing vascular morbidity and mortality. While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists show cardiovascular benefits in diabetes, their effects on PAD-related outcomes are unclear. This meta-analysis assessed the impact of these therapies on vascular outcomes in type 2 diabetes with PAD.

Recent Findings

A systematic review and meta-analysis were conducted per PRISMA guidelines (PROSPERO CRD420251083622). PubMed, Embase, and Cochrane Central were searched. A random-effects model pooled data. Primary outcomes were major adverse limb events, peripheral revascularization, and amputation. Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction, stroke, HbA1c, and weight changes. Six studies (four RCTs, two propensity score-matched cohorts) with 25,866 patients were included. Incretin-based therapies significantly reduced all-cause mortality (RR 0.52 [0.28–0.95], p = 0.032) and HbA1c (MD − 0.73% [–1.32 to − 0.15], p = 0.013) compared to placebo or standard care. No significant differences were found for major adverse limb events, revascularization, amputation, MACE, myocardial infarction, or stroke. Heterogeneity and low evidence certainty were noted.

Graphical Abstract

Summary of a systematic review and meta-analysis evaluating glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptoragonists in patients with type 2 diabetes mellitus (T2DM) and peripheralartery disease (PAD). Outcomes included mortality, major adverse limb events, peripheral revascularization, amputation, myocardial infarction(MI), major adverse cardiovascular events (MACE), stroke, and glycemic control. Results demonstrated reduced mortality and improved glycemiccontrol with incretin-based therapy, while limb-related outcomes andcardiovascular endpoints showed no statistically significant differences.GLP-1 = glucagon-like peptide-1; GIP = glucose-dependent insulinotropicpolypeptide; T2DM = type 2 diabetes mellitus; PAD = peripheral arterydisease; RCTs = randomized controlled trials; PSM = propensity-scorematched studies; RR = risk ratio; HR = hazard ratio; MD = meandifference; CI = confidence interval; I² = heterogeneity index; MACE =major adverse cardiovascular events; MI = myocardial infarction; HbA1c= glycated hemoglobin. Illustration created with Biorender