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Phase 3 N=792 Randomized Quadruple-blind Treatment

A Research Study to Compare a Medicine Called Semaglutide Against Placebo in People With Peripheral Arterial Disease and Type 2 Diabetes

Diabetes Mellitus, Type 2 · Peripheral Arterial Disease

Enrolled (actual)
792
Serious AEs
19.2%
Results posted
Jul 2025
Primary outcome: Primary: Change in Maximum Walking Distance on a Constant Load Treadmill Test — 1.21; 1.08 Ratio of maximum walking distance — p=0.0004

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Semaglutide (Drug); Placebo (semaglutide) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Novo Nordisk A/S
Primary completion
Jun 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Maximum Walking Distance on a Constant Load Treadmill Test
1.21; 1.08 0.0004 sig
SECONDARY
Follow-up Change in Maximum Walking Distance on a Constant Load Treadmill Test
1.16; 1.10 0.0380 sig
SECONDARY
Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) Score
2.0; 1.0 0.0108 sig
SECONDARY
Change in Pain-free Walking Distance on a Constant Load Treadmill Test
1.21; 1.10 0.0046 sig
SECONDARY
Follow-up Change in Pain-free Walking Distance on a Constant Load Treadmill Test
1.18; 1.10
SECONDARY
Change in Glycosylated Haemoglobin (HbA1c)
-0.8; 0.2
SECONDARY
Change in Body Weight
-5.2; -1.2
SECONDARY
Change in Systolic Blood Pressure
-4; -1
SECONDARY
Change in Total Cholesterol
0.96; 1.00
SECONDARY
Change in Low-density Lipoprotein (LDL)-Cholesterol
0.99; 1.03
SECONDARY
Change in High Density Lipoprotein (HDL)-Cholesterol
1.04; 0.99
SECONDARY
Change in Triglycerides
0.80; 0.95
SECONDARY
Change in Ankle-Brachial Index (ABI)
1.06; 1.02
SECONDARY
Change in Toe-Brachial Index (TBI)
1.07; 1.04
SECONDARY
Change in Walking Impairment Questionnaire (WIQ) Global Score
9.48; 6.51
SECONDARY
Change in Short Form 36 (SF-36) Physical Functioning Domain
2.98; 1.52

Summary

This study is done to see if semaglutide has an effect on walking ability compared with placebo (dummy medicine) in people with peripheral arterial disease (PAD) and type 2 diabetes. Participants will either get semaglutide or placebo ("dummy") medicine - which treatment participants get is decided by chance. Semaglutide is a medicine for type 2 diabetes that can be prescribed by doctors in some countries. Participants will get the study medicine (semaglutide or placebo) in a pre-filled pen for injection. Participants must inject it once a week into the stomach area, thigh, or upper arm, at any time of the day. The study will last for about 59 weeks. Participants will have 8 clinic visits and 1 phone call with the study doctor. At some clinic visits, participants will have blood tests. At some visits participants will also do a treadmill test to measure how far they can walk. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Eligibility Criteria

Inclusion Criteria

  • Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan: Male or female, age above or equal to 20 years at time of signing informed consent
  • Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.
  • Symptomatic PAD with intermittent claudication corresponding to Fontaine stage IIa (Rutherford classification grade I, category 1 and 2) meeting all of the following:
  • Stable symptoms of PAD with intermittent claudication in Fontaine stage IIa (able to walk without stopping more than 200 m/656 feet/2 blocks) for at least 90 days prior to the day of screening based on patient interview.
  • Screening flat treadmill test (3.2 km/h (2 mph)): Pain-free walking distance of at least 200 meters/656 feet.
  • Screening constant load treadmill test with fixed inclination of 12% and a fixed speed of 3.2 km/h (2 mph): Walking distance equal to or less than 600 meters/1968 feet.
  • Ankle-brachial-index (ABI) equal to or below 0.90 or toe-brachial index (TBI) equal to or below 0.7 (the leg with lowest index is chosen in case of bilateral disease).

Exclusion Criteria

  • Current or previous treatment with any GLP-1 receptor agonist (GLP-1-RA) within 90 days prior to the day of screening.
  • Walking ability limited by conditions other than PAD (e.g. aortic aneurism, dysregulated arrhythmia or hypertension, angina pectoris, heart failure, chronic obstructive or restrictive pulmonary disease, Parkinson's disease, severe peripheral neuropathy, amputations, wheel chair or walker dependency, osteoarthritis, morbid obesity, severe varicose veins, etc.).
  • Planned orthopaedic surgery in the legs, or other major surgery known on the day of screening (surgery affecting walking ability).
  • Vascular revascularisation procedure of any kind 180 days prior to the day of screening.
  • Planned arterial revascularisation known on the day of screening.
  • Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within 180 days prior to the day of screening.
  • Heart failure presently classified as being in New York Heart Association (NYHA) class III-IV.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04560998). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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