Pleiotropic effects of GLP‐1 receptor agonists on peripheral artery disease: Is there any hope?

Caruso, Paola; Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine; Giugliano, Dario

doi:10.1002/dmrr.3627

Cited by 6 publications

(11 citation statements)

References 34 publications

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“…Liraglutide, as well as other GLP-1RAs, may determine its effect on peripheral perfusion through both microvascular and macrovascular mechanisms. Liraglutide is effective on glycometabolic outlook, which affects the cardiovascular risk profile . Particularly, GLP-1RAs regulate glucose blood levels and peripheral insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Both preclinical and clinical studies have investigated the relationship among GLP-1RAs, vascular smooth muscle relaxation, and levels of inflammatory markers, including tumor necrosis factor α, plasminogen activator inhibitor 1, interleukin 1β, and interleukin 6, with a favorable effect on chronic systemic inflammation . Furthermore, the activation of the GLP-1 receptor may stimulate endothelial progenitor cells proliferation and differentiation, improving vascular homeostasis, angiogenesis, and plaque stability …”

Section: Discussionmentioning

confidence: 99%

“…28,29 Furthermore, the activation of the GLP-1 receptor may stimulate endothelial progenitor cells proliferation and differentiation, improving vascular homeostasis, angiogenesis, and plaque stability. 14,30 Peripheral artery atherosclerosis heavily contributes to lower-extremity complications and hospitalization, with high medical costs and severe clinical burden. 3 Moreover, PAD and its complications are responsible for the reduction of both life expectancy and quality, with a mortality rate that may overcome cancer mortality.…”

Section: Jama Network Open | Diabetes and Endocrinologymentioning

confidence: 99%

“…Moreover, a post hoc analysis from the LEADER (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes) trial described a significant reduction in lower-extremity amputations (hazard ratio, 0.65; 95% CI, 0.45-0.95; P = .03), mostly driven by major amputations rather than minor ones . This finding has been related to the liraglutide-induced improvement of several PAD risk factors as well as to pleiotropic effects that liraglutide may exert on the vascular system . Given its potential role in peripheral vascular disease, STARDUST (Effects of the GLP-1 Receptor Agonist Liraglutide on Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: An Open-Label Randomized Clinical Trial) was designed to assess the effect of daily administered liraglutide on peripheral perfusion in a population of individuals with type 2 diabetes and PAD.…”

Section: Introductionmentioning

confidence: 99%

“… 13 This finding has been related to the liraglutide-induced improvement of several PAD risk factors as well as to pleiotropic effects that liraglutide may exert on the vascular system. 10 , 14 Given its potential role in peripheral vascular disease, STARDUST (Effects of the GLP-1 Receptor Agonist Liraglutide on Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: An Open-Label Randomized Clinical Trial) was designed to assess the effect of daily administered liraglutide on peripheral perfusion in a population of individuals with type 2 diabetes and PAD.…”

Section: Introductionmentioning

confidence: 99%

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Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

Caruso,

Maiorino,

Longo

et al. 2024

JAMA Netw Open

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ImportancePeripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk.ObjectiveTo examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD.Design, Setting, and ParticipantsThis open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania “Luigi Vanvitelli,” Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included.InterventionsPatients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months.Main Outcomes and MeasuresCoprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group.ResultsFifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P &lt; .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P &lt; .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (−0.4 mg/dL; 95% CI, −0.7 to −0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (−119.4 mg/g; 95% CI, −195.0 to −43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P &lt; .001).Conclusions and RelevanceIn this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes.Trial RegistrationClinicalTrials.gov Identifier: NCT04881110

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Jama Network Open | Diabetes and Endocrinologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

Caruso,

Maiorino,

Longo

et al. 2024

JAMA Netw Open

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GLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease

Pan,

Chen,

Chen

et al. 2024

Nat Commun

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Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.

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Effect of the glucagon‐like peptide‐1 receptor agonists on diabetic peripheral neuropathy: A meta‐analysis

Fan,

Qiu,

Liu

et al. 2024

Journal of Neurochemistry

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Previous researches found that glucagon‐like peptide 1 receptor agonists (GLP‐1RA) offer benefits beyond their anti‐diabetic properties, including weight loss and cardiovascular disease prevention. However, the effects of GLP‐1RA on diabetic peripheral neuropathy (DPN) remain unclear. This meta‐analysis aims to assess the potential benefits of GLP‐1RA treatment in DPN patients by evaluating peripheral neural function. Following the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, we conducted a meta‐analysis of the clinical trials investigating the impact of GLP‐1RA treatment on peripheral neural function in patients with DPN. Outcomes were measured using electrophysiological tests, including nerve conduction velocity (NCV) and action potential amplitude. Our meta‐analysis included six studies with 271 participants. Following GLP‐1RA treatment, NCV significantly improved compared to the control group (MD 1.74; 95% CI 1.16 to 2.33; p < 0.001) and before treatment (MD 2.16; 95% CI 1.04 to 3.27; p < 0.001). Despite the improvement in NCV, blood glucose levels did not change significantly (MD −0.20 95% CI −0.87 to 0.46, p = 0.55) indicating that GLP‐1RA enhances NCV through mechanisms other than glucose lowering. Nonetheless, as a result of the limited population studied, further research is needed to strengthen the reliability of these findings.image

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Pleiotropic effects of GLP‐1 receptor agonists on peripheral artery disease: Is there any hope?

Cited by 6 publications

References 34 publications

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

GLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease

Effect of the glucagon‐like peptide‐1 receptor agonists on diabetic peripheral neuropathy: A meta‐analysis

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