Effect of Semaglutide on Healing of Foot Ulcers in Type 2 Diabetes Patients (SEMAFOOT2)

The SEMAFOOT2 Pilot Effect of Semaglutide on Healing of Foot Ulcers in Type 2 Diabetes Patients

The aim of this exploratory pilot study is to investigate the effect of semaglutide compared to placebo on healing of foot ulcers in type 2 diabetes patients.

It is a randomized double blind, placebo controlled, clinical intervention study of 20 weeks intervention.

Study Overview

• Status: Recruiting
• Conditions: Foot Ulcer Due to Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Semaglutide, 1.34 mg/mL; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ole L Svendsen, MD; Phone Number: +45 21830863; Email: ole.lander.svendsen@regionh.dk
• Study Contact Backup: Name: klaus Kirketerp-Møller, MD; Phone Number: +4538635134; Email: klaus.kirketerp-moeller.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Recruiting
    • Copenhagen Wound Healing Center, Bispebjerg University Hospital
    • Contact: Ole L Svendsen, MD; Phone Number: +45 21830863; Email: ole.lander.svendsen@regionh.dk
    • Contact: klaus Kirketerp-Møller, MD; Phone Number: +4538635134; Email: klaus.kirketerp-moeller.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of type 2 diabetes mellitus for at least 6 months
• Age 18-90 years
• A foot ulcer below the level of the malleoli. If more than one ulcer, the largest will be selected at screening as the index ulcer.
• Wound area after sharp debridement of ≥ 5 mm2, but ≤ 3000 mm2.

Exclusion Criteria:

• Current use, or recent use (<3 months), of GLP-1 agonists
• Current use of DPP-IV inhibitors
• Previous acute pancreatitis
• Signs of infection of the index ulcer
• Toe blood pressure < 40 mmHg at the foot with the index ulcer
• Current treatment with cytotoxic drugs or with systemically administered glucocorticoids
• Hospitalisation for a major cardiovascular event or procedure or revascularization surgery on a leg in the last 3 months, or scheduled major cardiovascular intervention
• Contraindication/intolerance to study medication
• Pre-existing medical condition judged to preclude safe participation in the study
• Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol
• Recent use (< 3 months) of an investigational drug or participation in interventional clinical foot ulcer-healing trial
• Known pregnancy, breast feeding or planning pregnancy.
• Women of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) without a confirmed menstrual period or with a positive highly sensitive pregnancy test).
• Women of childbearing potential not using highly effective birth control methods, such as combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence).
• Men, with female partners of childbearing potential, not vasectomised or not using condoms or sexual abstinence AND the female partner not using highly effective birth control, such as combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion).
• Likely inability to comply with the need for weekly visits because of planned activity
• Mental incapacity, unwillingness, not speaking and understanding Danish or language barrier precluding adequate understanding or cooperation
• Unable to provide written and signed informed consent.
• Use of any drug which in the Investigator's opinion could interfere with the healing of foot ulcers.
• Any clinically significant disease or disorder, except for conditions associated to the type 2 diabetes, which in the Investigator's opinion could interfere with the results of the trial
• Active cancer or a history of cancer in the 3 years prior to signing the informed consent form (history of basal cell carcinoma is allowed).
• Life expectancy of less than 12 months.
• Wounds caused primarily by untreated vascular insufficiency, or where patients are primarily eligible for vascular intervention to promote wound healing.
• Wounds with an etiology not related to diabetes.
• Underlying osteomyelitis of the leg with the wound to be treated.
• Patients presenting with the clinical characteristics of cellulitis at the wound site (suppurative inflammation involving particularly the subcutaneous tissue, often mild erythema, tenderness, malaise, chills and fever).
• Surgery to lengthen Achilles tendon on the leg with the wound to be treated 3 months prior to signing the informed consent form.
• Necrosis, purulence, or sinus tracts that cannot be removed by debridement on foot to be treated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: semaglutide; Ozempic® (semaglutide), which comes in prefilled pens, is approved for treatment of adults with insufficiently controlled type 2 diabetes mellitus. This group is treated with semaglutide 1 mg once weekly, with the usual starting dose of injection 0.25 mg semaglutide subcutaneously once weekly (OW). After four weeks the dose will be increased to 0.5 mg OW, and after another four weeks, the dose will be increased to 1.0 mg OW, depending on side effects. Novo Nordisk A/S will deliver the IP and will do so in a way that enables double blind treatment. The strength of the active IP used in this study is semaglutide 1.34 mg/ml.	Drug: Semaglutide, 1.34 mg/mL; pen for subcutaneous injections; Other Names: ozempic
Placebo Comparator: Placebo; The placebo group will receive blinded injection placebo subcutaneously once weekly, up titrated like semaglutide, as described above	Drug: Placebo; pen for subcutaneous injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of clinical healed index foot ulcer at week 20	Difference between the groups treated with semalutide and with placeebo in proportion of index ulcers completely healed after 20 weeks of intervention. Assessment of complete ulcer healing by naked eye will be performed by trained study staff: Total closure/healed (total epithelization): Yes or No. Complete ulcer healing is defined (as by FDA) as complete skin re-epithelialization without drainage or dressing requirements, confirmed at two consecutive study visit two weeks apart, and the time encountered as healed is the first of the two visits.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ulcer area after 20 weeks of intervention	Difference between the groups treated with semalutide and with placebo in change in ulcer area after 20 weeks of intervention. The index ulcers will be photographed using a standard camera. The distance from the ulcer will be appriximately 30 cm and a standard setting will be used for each photograph. A reference ruler will be included in the photograph and located beside the ulcer. The ulcer will be photographed 3 times and stored electronically. The ulcer area will be analyzed using ImageJ software v 1.47 (NIH).	20 weeks
Change in ulcer area from time of randomization until 8 and 16 weeks of intervention	Difference between the groups treated with semalutide and with placebo in index ulcer area. The index ulcers will be photographed using a standard camera. The distance from the ulcer will be approximately 30 cm and a standard setting will be used for each photograph. A reference ruler will be included in the photograph and located beside the ulcer. The ulcer will be photographed 3 times and stored electronically. The ulcer area will be analyzed using ImageJ software v 1.47 (NIH).	8 and 16 weeks
Change in distal blood pressure from time of randomization until after 20 weeks of intervention	Difference between the groups treated with semalutide and with placebo	20 weeks

Collaborators and Investigators

• Sponsor: Ole Lander Svendsen
• Investigators: Study Chair: Ole L Svendsen, MD, University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: semaglutide; randomized clinical trial; diabetic foot ulcer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Skin and Connective Tissue Diseases; Diabetic Foot; semaglutide
• Other Study ID Numbers: CODIF-015; 2023-504913-65-01 (Ctis); U1111-1282-3930 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No