The Efficacy, Mechanism & Safety of Sodium Glucose Co-Transporter-2 Inhibitor & Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Kidney Transplant Recipients

NCT05938712 | Recruiting Phase 2

• 1 other identifier: 23-5050
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to determine the short-term efficacy, mechanisms and safety of 12 weeks of dapagliflozin and semaglutide combination therapy in 20 KTR, with and without T2D.

Conditions

Kidney Transplant Recipients

Keywords

Type 2 diabetes; SGLT2 inhibition; GLP-1 receptor agonist

Outcome Measures

Primary Outcomes (2)

• Proximal tubular natriuresis with combination therapy

  Measured by fractional excretion of sodium

  From baseline to combination therapy end (24 weeks)

• Proximal tubular natriuresis with monotherapy

  Measured by fractional excretion of sodium

  From baseline to monotherapy end (12 weeks)

Secondary Outcomes (19)

• Measured Glomerular Filtration Rate

  From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

• Estimated Glomerular Filtration Rate

  From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

• Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration

  From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

• Urinary albumin excretion

  From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

• Arterial stiffness

  From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

Study Arms (2)

Semaglutide

EXPERIMENTAL

Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks.

Drug: Dapagliflozin 10 MG; Drug: Semaglutide, 1.0 mg/mL

Dapagliflozin

EXPERIMENTAL

Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks

Drug: Dapagliflozin 10 MG; Drug: Semaglutide, 1.0 mg/mL

Interventions

Dapagliflozin 10 MG DRUG

Semaglutide subcutaneous once weekly for 12 weeks.

Also known as: FARXIGA

Dapagliflozin; Semaglutide

Semaglutide, 1.0 mg/mL DRUG

Dapagliflozin oral once daily for 12 weeks.

Also known as: OZEMPIC

Dapagliflozin; Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent.
• Patients aged ≥18 years with KTR
• \>3 months post kidney transplantation
• Estimated glomerular filtration rate \[eGFR\] ≥20 ml/min/1.73m2
• BP \<160/100 and \>90/60 at screening
• Body-mass index \[BMI\] between 18.5-40kg/m2
• In patients with T2D or PTDM, HbA1c \<12.0%;

You may not qualify if:

• Type 1 diabetes.
• History of multi-organ transplant
• Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
• Impending need for kidney biopsy or rapid decline in eGFR within 30 days prior to screening
• Actively treated BK, CMV or EBV infection
• Recurrent pyelonephritis or need for indwelling or self-catheterization
• Prior amputation or ischemic rest pain
• Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial.
• History of pancreatitis
• Personal or family history or medullary thyroid cancer or MEN2B
• History of unstable diabetic retinopathy within 1 year prior to screening
• Use of SGLT2i or GLP-1RA within 30 days prior to screening.
• Current and frequent episodes of hypoglycemia
• Current history of DKA requiring medical intervention or hospitalization
• With current risk of volume depletion, hypotension and/or electrolyte imbalance

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Sunita Singh, MD MSc FRCPC

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vesta Lai

CONTACT

416-340-4800; vesta.lai@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Model Details: Patients will be allocated to treatment with either dapagliflozin 10 mg PO daily alone for 12 weeks or subcutaneous once weekly semaglutide up-titrated as tolerated every 4 weeks starting with 0.25 mg, then to 0.5 mg to 1 mg alone for 12 weeks, followed by a subsequent treatment period of combination therapy with dapagliflozin 10 mg PO daily plus maximally tolerated dose semaglutide (up-titrated every 4 weeks from 0.25 mg to 0.5 mg to 1 mg) subcutaneous once weekly.

Study Record Dates

• First Submitted: May 16, 2023
• First Posted: July 10, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)