Design and baseline characteristics of the STRIDE trial: evaluating semaglutide in people with symptomatic peripheral artery disease and type 2 diabetes

Eur Heart J Cardiovasc Pharmacother. 2025 Jan 11;10(8):728-737. doi: 10.1093/ehjcvp/pvae071.

Abstract

Background: People with lower extremity peripheral artery disease (PAD) suffer from a high burden of symptoms and significant functional impairment. There are few therapies that improve function and reduce symptoms in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycaemic control, reduce body weight, and reduce the risk of major adverse cardiovascular events in people with atherosclerotic cardiovascular disease and type 2 diabetes (T2D).

Methods and results: STRIDE (NCT04560998) is a randomized, placebo-controlled, double-blind phase 3b trial evaluating 1 mg once-weekly subcutaneous semaglutide (GLP-1 RA) vs. placebo, in people with symptomatic PAD (Fontaine IIa claudication) and T2D. Eligible participants were ≥18 years, had haemodynamically stable PAD, had no planned intervention, and were not receiving a GLP-1 RA. The primary endpoint is change in maximum walking distance on a constant-load treadmill (CLT). Secondary endpoints include quality of life and cardiometabolic assessments. A total of 792 participants were randomized in 20 countries. Participants' median age was 68 and median T2D duration 12 years. Risk factors included 25.6% current smokers, 87.9% with hypertension, and 42.7% with coronary heart disease. The mean BMI was 29.6 kg/m2 and the mean HbA1C was 7.3%. Participants exhibited baseline functional impairment with a median maximum walking distance of 186 m on a CLT.

Conclusion: STRIDE has enrolled participants with symptomatic PAD and T2D, frequent risk factors and comorbidities, and functional impairment. The trial will provide evidence for the functional outcomes with semaglutide in people with PAD and T2D.

Keywords: GLP1 agonist; Maximal walking distance; PAD; Peripheral artery disease; Semaglutide.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Clinical Trial Protocol

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Europe / epidemiology
  • Exercise Tolerance / drug effects
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptides* / administration & dosage
  • Glucagon-Like Peptides* / adverse effects
  • Glucagon-Like Peptides* / therapeutic use
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Incretins / adverse effects
  • Incretins / therapeutic use
  • Injections, Subcutaneous
  • Intermittent Claudication / diagnosis
  • Intermittent Claudication / drug therapy
  • Intermittent Claudication / physiopathology
  • Male
  • Middle Aged
  • Peripheral Arterial Disease* / diagnosis
  • Peripheral Arterial Disease* / drug therapy
  • Peripheral Arterial Disease* / physiopathology
  • Quality of Life*
  • Recovery of Function
  • Time Factors
  • Treatment Outcome
  • Walk Test

Substances

  • semaglutide
  • Glucagon-Like Peptides
  • Hypoglycemic Agents
  • Incretins
  • Biomarkers
  • Glucagon-Like Peptide-1 Receptor
  • GLP1R protein, human
  • Blood Glucose

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