<div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1729114166" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{13}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">GLP-1 receptor agonists were associated with lower rates of death and limb complications in people with both peripheral artery disease (PAD) and type 2 diabetes, according to<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">a<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">new analysis</span><span class="NormalTextRun SCXW15529078 BCX0">.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="419544742" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{15}"><span class="NormalTextRun SCXW15529078 BCX0">The study compared matched patients receiving GLP-1 receptor agonists with matched patients receiving metformin and found lower five-year rates of several major outcomes. </span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="942894015" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{17}"><span class="NormalTextRun SCXW15529078 BCX0">In the overall PAD cohort, mortality was 10.31% with GLP-1 therapy versus 14.49% with metformin, while major amputation was 2.30% versus 4.36%. </span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1233215938" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{19}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">Hospitalization,<span> </span></span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW15529078 BCX0">revascularization</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>and minor amputation were also significantly lower, although myocardial infarction, stroke, major adverse cardiovascular<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">events</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>and major adverse kidney events were similar between groups.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1495900010" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{21}"><strong><span class="NormalTextRun SCXW15529078 BCX0">Vascular effects</span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1163816978" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{23}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">“</span><span class="NormalTextRun SCXW15529078 BCX0">…</span><span class="NormalTextRun SCXW15529078 BCX0">GLP-1 RAs have been shown to exert direct vascular effects, including enhancement of endothelial function, reduction in oxidative stress, and attenuation of vascular inflammation</span><span class="NormalTextRun SCXW15529078 BCX0">,”</span><span> </span><span class="NormalTextRun SCXW15529078 BCX0">wrote the researchers, led by<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">Akiva Rosenzveig, MD, from the Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="170845749" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{25}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">“</span><span class="NormalTextRun SCXW15529078 BCX0">These agents improve nitric oxide bioavailability and reduce the expression of proinflammatory cytokines such as IL-6 (interleukin-6) and TNF-α (tumor necrosis factor alpha), thereby promoting vasodilation and reducing endothelial injury.”</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1141306413" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{27}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">The study</span><span class="NormalTextRun SCXW15529078 BCX0">, which is<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">published in the<span> </span></span></span><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><em><span class="NormalTextRun SCXW15529078 BCX0">Journal of the American Heart Association</span></em><span class="NormalTextRun SCXW15529078 BCX0">,<span> </span></span></span><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">d</span><span class="NormalTextRun SCXW15529078 BCX0">r</span><span class="NormalTextRun SCXW15529078 BCX0">e</span><span class="NormalTextRun SCXW15529078 BCX0">w</span><span> </span><span class="NormalTextRun SCXW15529078 BCX0">on data from the<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW15529078 BCX0">TriNetX</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>federated health research network,<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">where<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">the team assessed patients treated over a 15-year period, from January 2010 to January 2025. </span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="756449557" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{29}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">The analysis excluded patients with recent myocardial infarction, stroke, end-stage renal<span> </span></span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW15529078 BCX0">disease</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>or prior amputations, while<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">propensity score matching was used to help balance key baseline factors between the groups.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1355610204" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{31}"><strong><span class="NormalTextRun SCXW15529078 BCX0">Greatest limb risk</span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1153849733" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{33}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">The association was particularly<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">evident</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>in patients at greatest limb risk, including those with chronic limb-threatening ischemia.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1592513365" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{35}"><span class="NormalTextRun SCXW15529078 BCX0">GLP-1 therapy was associated with lower rates of death, hospitalization, revascularization and both major and minor amputation. </span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="149531416" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{37}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">In patients with claudication, the pattern was narrower, with reductions seen for mortality,<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">hospitalization</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>and major amputation, but not for myocardial infarction,<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">stroke</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>or revascularization.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1367259039" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{39}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">“</span><span class="NormalTextRun SCXW15529078 BCX0">Lastly, although we report significant associations with lower rates of adverse outcomes, the study is not designed to establish causality</span><span class="NormalTextRun SCXW15529078 BCX0">,” wrote the researchers.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1648452717" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{41}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">“</span><span class="NormalTextRun SCXW15529078 BCX0">Despite careful matching and robust analytic techniques, randomized controlled trials remain the gold standard for evaluating therapeutic efficacy.”</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="13983151" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{43}"><strong><span class="NormalTextRun SCXW15529078 BCX0">Further trials</span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1419545329" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{45}"><span class="NormalTextRun SCXW15529078 BCX0">The results add to growing interest in GLP-1 receptor agonists as therapies that may do more than improve glycemic control and weight management. </span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="980631375" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{48}"><span class="NormalTextRun SCXW15529078 BCX0">The authors said the drugs could have a disease-modifying role in PAD, particularly among patients with coexisting diabetes. </span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1883431228" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{50}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">However, because the analysis was retrospective and observational, further randomized trials will be needed to<span> </span></span><span class="NormalTextRun SCXW15529078 BCX0">determine</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>whether GLP-1 therapy itself reduces amputations, limb<span> </span></span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW15529078 BCX0">procedures</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>and deaths over the long term.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="1597356532" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{52}"><strong><span class="NormalTextRun SCXW15529078 BCX0">Source:</span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" paraid="716391590" paraeid="{ce284713-b0cc-4e26-b489-0d13d94665c7}{54}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0">Rosenzveig A, Tefera L, Agrawal A, et al. Long-Term Outcomes of Glucagon-Like Peptide-1 Receptor Agonists in Patients<span> </span></span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW15529078 BCX0">With</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>Peripheral Artery Disease and Type 2 Diabetes.<span> </span></span></span><span class="NormalTextRun SCXW15529078 BCX0"><em>J Am Heart</em> <em>Assoc</em>.</span><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW15529078 BCX0"><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>2026</span><span class="NormalTextRun SCXW15529078 BCX0"><span> </span>July (Article in Press)</span><span class="NormalTextRun SCXW15529078 BCX0">.</span></span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></p> </div> <div class="OutlineElement Ltr SCXW15529078 BCX0"> <p class="Paragraph SCXW15529078 BCX0" lang="EN-US" paraid="1289737393" paraeid="{6d29f4d9-bc1d-4863-99b6-3c0a19c9fa0b}{41}"><strong><span class="NormalTextRun SCXW15529078 BCX0">Image Credit: Kateryna – stock.adobe.com</span><span class="EOP Selected SCXW15529078 BCX0" data-ccp-props="{"335551550":6,"335551620":6}"> </span></strong></p> </div>