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

NCT ID: NCT04560998

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 792 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2024-07-12

Brief 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.

Conditions

Diabetes Mellitus, Type 2; Peripheral Arterial Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Semaglutide

Semaglutide given in addition to standard-of-care treatment

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Semaglutide is administered subcutaneously (s.c.; under the skin) once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.

Placebo (semaglutide)

Placebo given in addition to standard-of-care treatment

Group Type: PLACEBO_COMPARATOR

Placebo (semaglutide)

Intervention Type: DRUG

Placebo (semaglutide) is administered s.c. once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.

Interventions

Semaglutide

Semaglutide is administered subcutaneously (s.c.; under the skin) once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.

Intervention Type: DRUG

Placebo (semaglutide)

Placebo (semaglutide) is administered s.c. once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.

Intervention Type: DRUG

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:

1. 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.

2. Screening flat treadmill test (3.2 km/h (2 mph)): Pain-free walking distance of at least 200 meters/656 feet.

3. 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.

4. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency (1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Cardiology, PC

Birmingham, Alabama, United States

Central Arkansas Veteran's Healthcare System

Little Rock, Arkansas, United States

Cardio Innovation & Resch Ctr

Long Beach, California, United States

Angel City Research, Inc.

Los Angeles, California, United States

St. Joseph Heritage Healthcare_Mission Viejo

Mission Viejo, California, United States

Rocky Mount Reg VA Med-DN

Aurora, Colorado, United States

Univ of Colorado at Denver

Aurora, Colorado, United States

Bay Area Cardiology Associates, P.A.

Brandon, Florida, United States

Clearwater Cardiovascular Consultants

Clearwater, Florida, United States

Tampa Bay Medical Research

Clearwater, Florida, United States

Jacksonville Ctr For Clin Res

Jacksonville, Florida, United States

DMI Research

Pinellas Park, Florida, United States

University of South Florida

Tampa, Florida, United States

Accel Research Site-Georgia

Eatonton, Georgia, United States

Reg Infectious Dis Infuse Ctr

La Grange, Georgia, United States

Aiyan Diabetes Center

Martinez, Georgia, United States

Endeavor Health Glenbook Hosp

Glenview, Illinois, United States

Central IL Diabetes and Clinical Research

Springfield, Illinois, United States

Cardiovascular Rsrch of NW_IN

Munster, Indiana, United States

Central Cardio Assoc HPS

Elizabethtown, Kentucky, United States

Cambridge Medical Trials

Alexandria, Louisiana, United States

LOUISIANA HEART Center

Covington, Louisiana, United States

Clinical Trials of Ame, LLC

Monroe, Louisiana, United States

Ascension Saint Agnes Heart Ca

Baltimore, Maryland, United States

Boston Medical Center_Cary

Boston, Massachusetts, United States

Minneapolis Cardiology Assoc

Minneapolis, Minnesota, United States

Amicis Centers of Clinical Research

St Louis, Missouri, United States

Nebraska West Iowa Hlth System

Omaha, Nebraska, United States

Methodist Phys Clin Heart Cons

Omaha, Nebraska, United States

Dartmouth-Hitchcock Med Ctr

Lebanon, New Hampshire, United States

NYU Langone Med Assoc Chelsea

New York, New York, United States

Accellacare_NC

Wilmington, North Carolina, United States

Capital Area Research LLC

Camp Hill, Pennsylvania, United States

Penn Presb Med Ctr

Philadelphia, Pennsylvania, United States

Vanderbilt U Med Ctr_Nashville

Nashville, Tennessee, United States

PharmaTex Research

Amarillo, Texas, United States

Northwest Houston Cardiology, P.A.

Houston, Texas, United States

Houston Heart & Vascular Associates

Humble, Texas, United States

Texas Cardiology Associates of Houston

Kingwood, Texas, United States

Texas Tech University Health Science Center

Lubbock, Texas, United States

North Dallas Research Associates

McKinney, Texas, United States

Victoria Heart and Vasc Ctr

Victoria, Texas, United States

Selma Medical Associates

Winchester, Virginia, United States

Universitätsklinik für Innere Medizin Graz

Graz, , Austria

Univ.-Klinik für Innere Medizin III

Innsbruck, , Austria

Klinik Landstraße

Vienna, , Austria

AKH Wien

Vienna, , Austria

Imeldaziekenhuis Bonheiden - Thoracic and Vascular Surgery

Bonheiden, , Belgium

Ziekenhuis Oost-Limburg AV - Thoracic

Genk, , Belgium

UZ Gent - Thoracale Vasculaire Heelkunde

Ghent, , Belgium

UZ Gent_Gent_1

Ghent, , Belgium

AZ Groeninge - Thoracic Vascular Surgery

Kortrijk, , Belgium

UZ Leuven - Hart en Vaatziekten

Leuven, , Belgium

North York Diagn & Cardiac Ctr

North York, Ontario, Canada

North York Diagnostic and Cardiac Centre

North York, Ontario, Canada

The Ottawa Hospital, Civic Campus

Ottawa, Ontario, Canada

ViaCar Recherche Clinique Inc

Brossard, Quebec, Canada

Ecogene-21

Chicoutimi, Quebec, Canada

Clinique Sante Cardio MC

Montreal, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

CISSS des Laurentides

Saint-Jérôme, Quebec, Canada

CHU de Quebec-Universite Laval

Québec, , Canada

Institut universitaire de cardiologie

Québec, , Canada

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, China

The First Bethune hospital of Jilin University-Endocrinology

Changchun, Jilin, China

The first hospital of Jilin University

Changchun, Jilin, China

1st Affiliated Hosp of Xi'an JiaoTong Uni Medical College

Xi'an, Shaanxi, China

The First Affiliated Hospital of Xi'an JiaoTong University-Cardiovascular

Xi'an, Shaanxi, China

Tianjin Union Medical Center-Cardiology

Tianjin, , China

Tianjin Union Medicine Centre

Tianjin, , China

CTC Hodonin s.r.o.

Hodonín, , Czechia

EDUMED Jaromer

Jaroměř, , Czechia

Kucera

Ostrava Dubina, , Czechia

Diabetologicka ambulance Plzen

Pilsen, , Czechia

II. interni klinika - klinika kardiologie a angiologie 1. LF

Prague, , Czechia

Kolding Sygehus Karkirurgi

Kolding, , Denmark

Rigshospitalet Karkirurgisk afd. RK 3111

København Ø, , Denmark

Hjerte-, Lunge- og Karkirurgisk afdeling T

Odense, , Denmark

Regionshospitalet Viborg - Karkirurgisk Afsnit

Viborg, , Denmark

Kardiologische Praxis

Bad Homburg, , Germany

Herz- und Diabeteszentrum NRW - Bad Oeynhausen

Bad Oeynhausen, , Germany

Kreutzmann

Dresden, , Germany

Uniklinik TU Dresden - Med. Klinik und Poliklinik III Angiologie

Dresden, , Germany

MVZ CCB Frankfurt und Main-Taunus GbR

Frankfurt, , Germany

Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck

Lübeck, , Germany

Universitätsmedizin der JGU Mainz - Kardiologie I

Mainz, , Germany

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

Münster, , Germany

Gemeinschaftspraxis Haggenmiller/Jeserich

Nuremberg, , Germany

Zentrum für klinische Studien Alexander Segner

Saint Ingbert-Oberwürzbach, , Germany

University Hospital of Athens ATTIKON

Athens, Attica, Greece

"Laiko" General Hospital of Athens

Athens, , Greece

Konstantopouleio G.H. of Athens, "Agia Olga"

Athens, , Greece

"Hygeia" General Hospital of Athens

Athens, , Greece

General Hospital of Chios "Skilitsio" - Cardiology Clinic

Chios, , Greece

General Hospital of Lamia

Lamia, , Greece

'Ippokrateio' General Hospital of Thessaloniki

Thessaloniki, , Greece

General Hospital of Thessaloniki "G.Papanikolaou"

Thessaloniki, , Greece

Szegedi Tudományegyetem II. sz Belgyógyászati és Kardiológia

Szeged, Csongrád-Csanád, Hungary

Léda Platán Magánklinika

Zalaegerszeg, Zala County, Hungary

Szent Margit Rendelőintézet Nonprofit Kft.

Budapest, , Hungary

Szent Imre Egyetemi Oktatókórház Angiológia

Budapest, , Hungary

Semmelweis Egyetem Városmajori Szív- és Érgyógyászat

Budapest, , Hungary

Coromed SMO Kft.

Pécs, , Hungary

Sanjeevani Superspeciality Hospital

Ahmedabad, Gujarat, India

Shri B D Mehta Mahavir Heart Institute

Surat, Gujarat, India

Shri B. D. Mehta Mahavir Heart Institute

Surat, Gujarat, India

Shri Krishna Hrudayalaya & Critical Care Centre

Nagpur, Maharashtra, India

Shrikrishna Hrudayalaya and critical care centre

Nagpur, Maharashtra, India

Vijan Hospital & Research Centre

Nashik, Maharashtra, India

VMMC & Safdarjung Hospital

New Dehli, New Delhi, India

SP Medical College

Bikaner, Rajasthan, India

Osmania General Hospital

Hyderabad, Telangana, India

Udyaan Health Care

Lucknow, Uttar Pradesh, India

Sir Ganga Ram Hospital

New Delhi, , India

New Tokyo Heart Clinic_Matsudo-shi, Chiba,

Chiba, , Japan

Akaicho Clinic

Chiba-shi, Chiba, , Japan

Takahashi Hospital_Cardiology

Hyōgo, , Japan

Higashi Takarazuka Satoh Hospital_Cardiology

Hyōgo, , Japan

Higashi Takarazuka Satoh Hospital

Hyōgo, , Japan

Naka Kinen Clinic_Internal medicine

Ibaraki, , Japan

Naka Kinen Clinic

Ibaraki, , Japan

Nishiyamado Keiwa Hospital_Internal Medicine

Ibaraki, , Japan

Omihachiman Community Medical Center_Omihachiman-shi, Siga

Omihachiman-shi, Siga, , Japan

Minamiosaka Hospital_Internal medicine

Osaka, , Japan

Saitama Cardiovascular and Respiratory Center

Saitama, , Japan

Omi Medical Center_Cardiovascular Medicine

Shiga, , Japan

Omi Medical Center

Shiga, , Japan

Minamino Cardiovascular Hospital_Cardiovascular medicine

Tokyo, , Japan

Stradini PAD

Riga, , Latvia

Hospital Universiti Sains Malaysia

Kota Bharu, Kelantan, Malaysia

University Malaya Medical Centre

Lembah Pantai, Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, Malaysia

Hospital Pulau Pinang

George Town, Pulau Pinang, Malaysia

University Technology MARA (UiTM) - Sg Buloh

Sungai Buloh, Selangor, Malaysia

National Heart Institute

Kuala Lumpur, , Malaysia

Hospital Queen Elizabeth II

Sabak Bernam, , Malaysia

Haukeland universitetssykehus - Karkirurgisk avdeling

Bergen, , Norway

Sørlandet sykehus HF Kristiansand

Kristiansand, , Norway

OUS, Aker

Oslo, , Norway

Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET

Krakow, Lesser Poland Voivodeship, Poland

UniCardia & UniMedica & UniEstetica

Krakow, , Poland

Centrum Medyczne OMEDICA

Poznan, , Poland

Velocity Nova Sp. z o.o.

Puławy, , Poland

Gabinety Lekarskie LabMed

Szczecin, , Poland

Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego

Warsaw, , Poland

DoktorA

Warsaw, , Poland

Centrum Badan Klinicznych

Wroclaw, , Poland

Multispecialty Medical Clinic Anturium LLC

Barnaul, , Russia

Road Clinical Hospital at station Chelyabinsk

Chelyabinsk, , Russia

Irkutsk State Medical Academy of Postgraduate Education

Irkutsk, , Russia

Limited Liability Company "Alliance Biomedical Ural Group"

Izhevsk, , Russia

SRMC "Your Health" LLC

Kazan', , Russia

FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia

Moscow, , Russia

Federal Bureau for Medical and Social Expertise

Moscow, , Russia

Pirogov Russian National Research Medical University MoH

Moscow, , Russia

LLC RC Medical

Novosibirsk, , Russia

SGIoH of Novosibirsk region "CC Hospital #19"

Novosibirsk, , Russia

State Novosibirsk regional clinical hospital

Novosibirsk, , Russia

LLC "Clinical diagnostic center Ultramed"

Omsk, , Russia

Ryazan State Medical University

Ryazan, , Russia

Joint Stock Company "Polyclinic Complex"

Saint Petersburg, , Russia

Limited Liability Company "Clinic" MEDINEF "

Saint Petersburg, , Russia

Limited Liability Company "Energiya Zdoroviya"

Saint Petersburg, , Russia

SGHI "Polyclinic #106"

Saint Petersburg, , Russia

Regional clinical cardiology dispensary

Saratov, , Russia

SHI Saratov City Clinical Hospital #9

Saratov, , Russia

Voronezh Regional Clinical Consultive-diagnostic Centre

Voronezh, , Russia

Polyclinic #2 in Yoshkar-Ola

Yoshkar-Ola, , Russia

Centro Periférico de Especialidades Bola Azul

Almería, , Spain

Hospital Reina Sofia

Córdoba, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Hospital Gregorio Marañón

Madrid, , Spain

Hospital Civil de Málaga

Málaga, , Spain

Hospital Virgen de la Macarena

Seville, , Spain

Hospital Vithas Sevilla

Seville, , Spain

Kärlkirurgen/kärllab

Gothenburg, , Sweden

Kärlmottagningen

Uppsala, , Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Kuang Tien General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital_main

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Medical Foundation - Linkou Branch

Taoyuan District, , Taiwan

Srinagarind Hospital

Muang, Changwat Khon Kaen, Thailand

King Chulalongkorn Memorial Hospital, Cardiology department

Bangkok, , Thailand

Phramongkutklao Hospital-cardio

Bangkok, , Thailand

Research Institute for Health Sciences, CMU

Chiang Mai, , Thailand

Rihes - Research Institute for Health Sciences

Chiang Mai, , Thailand

Srinagarind Hospital

Khon Kaen, , Thailand

Maharat Nakhon Ratchasima Hospital_Ratchasima

Nakhon Ratchasima, , Thailand

Maharat Nakhon Ratchasima Hospital_

Nakhon Ratchasima, , Thailand

Thammasat University Hospital_Pathumthani

Pathum Thani, , Thailand

Songklanagarind Hospital

Songkhla, , Thailand

Countries

United States; Austria; Belgium; Canada; China; Czechia; Denmark; Germany; Greece; Hungary; India; Japan; Latvia; Malaysia; Norway; Poland; Russia; Spain; Sweden; Taiwan; Thailand

References

Bonaca MP, Catarig AM, Houlind K, Ludvik B, Nordanstig J, Ramesh CK, Rasouli N, Sourij H, Videmark A, Verma S; STRIDE Trial Investigators. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. Lancet. 2025 May 3;405(10489):1580-1593. doi: 10.1016/S0140-6736(25)00509-4. Epub 2025 Mar 29.

Reference Type: DERIVED

PMID: 40169145 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-003399-38

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1238-7071

Identifier Type: OTHER

Identifier Source: secondary_id

NN9535-4533

Identifier Type: -

Identifier Source: org_study_id