{"id":138700,"date":"2025-03-29T17:02:02","date_gmt":"2025-03-29T21:02:02","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=138700"},"modified":"2026-01-28T17:58:37","modified_gmt":"2026-01-28T22:58:37","slug":"semaglutide-increased-walking-distance-in-patients-with-t2dm-and-symptomatic-pad","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=138700","title":{"rendered":"Semaglutide Increased Walking Distance in Patients with T2DM and Symptomatic PAD"},"content":{"rendered":"<p><span style=\"font-weight: 400;\">Key Points:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Patients with peripheral artery disease (PAD) in combination with type 2 diabetes (T2D) suffer from significant functional limitations and limited treatments.<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">GLP-RA medications have demonstrated benefits that may target the pathobiology of PAD.<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">In STRIDE, semaglutide was compared with placebo in patients with T2D and early symptomatic PAD.<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Semaglutide was associated with a significant improvement in maximum walking distance, pain free walking distance, quality of life, ankle brachial index, and disease progression.<\/span><\/li>\n<\/ul>\n<p><!--more--><\/p>\n<p><span style=\"font-weight: 400;\">Peripheral artery disease (PAD) is a prevalent and morbid manifestation of atherosclerotic cardiovascular disease and is the most frequent first manifestation of cardiovascular disease in patients with type 2 diabetes (T2D). PAD in combination with T2D is a particular clinical challenge, more likely to be a small vessel disease and occur below the knee, with limited management options. Among this population, functional impairment is significant. It has been a quarter of a century since cilostazol was approved for treatment of functional impairment in PAD. Cilostazol is infrequently used due to its poor tolerability profile, heart failure contraindication, and having no additional cardiovascular benefits, but currently stands as the only class 1 guideline-recommended treatment for claudication &#8211; leg pain with walking &#8211; as it demonstrated a ~40 meter mean improvement on treadmill distance. SGLT2i and GLP-RA medications are class 1 guideline-recommended for T2D, however no agent is prioritized on the basis of PAD-specific benefits. GLP-RA medications have a broad range of benefits that theoretically target the pathobiology of PAD including anti-inflammatory effects, metabolic improvement, and in one trial, a reduction in amputations associated to diabetic foot ulcer. In a late breaking clinical trial presented at the 2025 American College of Cardiology Scientific Sessions on Saturday, March 29, Dr. Marc Bonaca on belhalf of the STRIDE Trial Investigators presented findings from the <\/span><a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(25)00509-4\/abstract\"><span style=\"font-weight: 400;\">STRIDE<\/span><\/a><span style=\"font-weight: 400;\"> trial: \u201cSemaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes: A Randomized, Double -Blind, Phase 3 Trial.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">STRIDE (NCT04560998) is a phase 3b randomized, placebo- controlled, double blind trial of 52 weeks of semaglutide 1 mg vs placebo in people with T2D and early-stage symptomatic PAD. Eligibility criteria included T2D diagnosis \u2265180 days prior to screening, early-stage symptomatic PAD (Fontaine stage IIa), pain free walking distance \u2265200 m on a flat treadmill test, and maximum walking distance \u2264600 m on a constant load treadmill test. Key exclusion criteria were unstable cardiovascular condition or plan for revascularization.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">The primary endpoint was change in maximum walking distance (MWD) at week 52. Key pre-specified secondary and exploratory outcomes were Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score, pain-free walking distance (PFWD), ankle brachial index (ABI), an anchor measure to assess clinically meaningful change in the primary endpoint, and clinical outcomes measured by progression to rescue treatment, major adverse limb event, or mortality.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">A total of 792 participants were randomized in 20 countries (mean: age 67 yrs; body mass index 29.6 kg\/m2). One-third of patients had a BMI &lt;27 and two-thirds of patients were current or former smokers. Mean ABI was 0.75, however these patients were severely disabled with a baseline median MWD of 186 m, only one-tenth of a mile.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">In an intention-to treat-analysis, semaglutide was superior for the primary endpoint with the difference apparent at six months and the curves continuing to separate through one year (estimated treatment ratio 1.13; p&lt;0.001). The benefit was consistent across age, sex, HbA1c, and, importantly, BMI. Median MWD difference vs placebo at week 52 was 26.4 m (95% CI [11.8-40.9]) and mean difference was 39.9 m (95% CI [13.9-66.0]). The prespecified anchor endpoint was significant, demonstrating a clinically meaningful benefit. Semaglutide was superior for secondary endpoints including PFWD (estimated treatment ratio 1.11, 95% CI [1.03-1.20]; p=0.0046), VascuQoL-6 (estimated treatment difference 1.00, 95% CI [0.48-1.52]; p=0.011), and ABI (estimated treatment ratio 1.05, 95% CI [1.02-1.09]; p=0.0037). Composite progression to adverse clinical outcome was superior with semaglutide (HR 0.46, 95% CI [0.24-0.85]). Safety aligned with previous semaglutide trials, including increased occurrence of gastrointestinal events and decreased appetite. In an exploratory analysis, semaglutide showed a 54% reduction in rescue initiation, MALE and mortality compared to placebo<\/span><\/p>\n<p><span style=\"font-weight: 400;\">When concluding his discussion at the ACC conference, Dr. Bonaca stated: \u201cWe know there are a breadth of benefits with semaglutide including cardiometabolic benefits, reductions in major adverse cardiovascular events, and improvements in kidney outcomes. Now, from STRIDE, we know that in patients with symptomatic PAD, semaglutide significantly improves function in a clinically meaningful way. It improves symptoms and quality of life, reduces disease progression, improves ABI, and with a safety profile consistent to prior studies\u2026We have a new drug for peripheral artery disease.\u201d\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points: Patients with peripheral artery disease (PAD) in combination with type 2 diabetes (T2D) suffer from significant functional limitations and limited treatments. GLP-RA medications have demonstrated benefits that may target the pathobiology of PAD. In STRIDE, semaglutide was compared with placebo in patients with T2D and early symptomatic PAD. Semaglutide was associated with a [&hellip;]<\/p>\n","protected":false},"author":40621,"featured_media":7215,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[898,8],"tags":[899,45,47],"ppma_author":[1077],"class_list":{"0":"post-138700","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-acc-2025","8":"category-news","9":"tag-acc-2025","10":"tag-conference","11":"tag-featured","12":"author-jessie-fox-md"},"authors":[{"term_id":1077,"user_id":40621,"is_guest":0,"slug":"jessie-fox-md","display_name":"Jessie Fox MD","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138700","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40621"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138700"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138700\/revisions"}],"predecessor-version":[{"id":138701,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138700\/revisions\/138701"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/7215"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138700"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138700"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138700"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138700"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}