HALLMARK

RecruitingPhase 2

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

A Two Arm, Open Label, Pilot Study to Evaluate the Safety and Efficacy of the Combined Use of Once Daily 10mg Dapagliflozin and Once Weekly 1.0mg Semaglutide in Kidney Transplant Recipients

Lead sponsor

University Health Network, Toronto

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Chronic kidney disease

Key I/E criteria

•BMI 18.5-40•HbA1c ≤12%•eGFR ≥20

Primary endpoints

•Proximal tubular natriuresis with combination therapy•Proximal tubular natriuresis with monotherapy

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05938712

Org study ID23-5050

Timeline

Milestones

Study first posted2023-07-10actual

Study start2023-10-24actual

Last update posted2026-05-01actual

Primary completion2027-10-01estimated

Study completion2028-03-01estimated

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Chronic kidney disease

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•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%;

Exclusion criteria

•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

•With known or suspected hypersensitivity to semaglutide or related products

•Patient not able to understand and comply with study requirements, based on Investigator's judgment.

•Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome etc.).

Endpoints (21)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Renal / kidney

Weight & body composition

Glycemic / diabetes

Cardiometabolic biomarkers

MASH / liver

Other (unclassified)

Weight & body composition

2 endpoints

Secondary/protocol endpoint

Change in body composition (percent body mass, body fat, and muscle mass)

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

percent change from baseline, improvement

Secondary/protocol endpoint

Change in body weight

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

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Change in percentage of glycated hemoglobin (HbA1c)

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

HbA1c, % change

percent change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint/low confidence

Change in concentration of urine glucose excretion

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

change from baseline, improvement

MASH / liver

1 endpoint

Secondary/protocol endpoint

Liver stiffness

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

Liver stiffness (VCTE), change

change from baseline, improvement

Renal / kidney

5 endpoints

Primary/protocol endpoint/low confidence

Proximal tubular natriuresis with combination therapy

Time frame:From baseline to combination therapy end (24 weeks)

change from baseline, improvement

Primary/protocol endpoint

Proximal tubular natriuresis with monotherapy

Time frame:From baseline to monotherapy end (12 weeks)

change from baseline, improvement

Secondary/protocol endpoint

Measured Glomerular Filtration Rate

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

eGFR, change

change from baseline, improvement

Secondary/protocol endpoint

Estimated Glomerular Filtration Rate

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

eGFR, change

change from baseline, improvement

Secondary/protocol endpoint

Urinary albumin excretion

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

change from baseline, improvement

Cardiometabolic biomarkers

2 endpoints

Secondary/protocol endpoint/low confidence

Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration

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

concentration, descriptive

Secondary/protocol endpoint

Arterial stiffness

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

change from baseline, improvement

Safety / tolerability / PK

8 endpoints

Secondary/protocol endpoint

Safety: the incidence of acute kidney injury.

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

event count, event

Secondary/protocol endpoint/low confidence

Safety: the incidence of hypotension

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

time to event, event

Secondary/protocol endpoint

Safety: The incidence of hyperkalemia

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

event count, event

Secondary/protocol endpoint

Safety: The incidence of urinary and mycotic infections.

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

event count, event

Secondary/protocol endpoint

Safety: The number of ketoacidosis events.

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

event count, event

Secondary/protocol endpoint

Safety: The incidence of amputations.

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

event count, event

Secondary/protocol endpoint

Safety: The incidence of pancreatitis or biliary complications

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

composite event, event

componentsPancreatitis, Gallbladder event

Secondary/protocol endpoint

Safety: The number of allergic reaction events.

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

event count, event

Other (unclassified)

1 endpoint

Secondary/protocol endpoint/low confidence

Diastolic function

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

descriptive

Publications (5)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Deep learning-enhanced 3D imaging unveils semaglutide impact on cardiac fibrosis.
British journal of pharmacology2026 Mar (month)PMID41121520doi:10.1111/bph.70217via pubmed acronym asset candidate
Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice.
Cell reports. Medicine2023 Sep 19PMID37729871doi:10.1016/j.xcrm.2023.101193via pubmed acronym asset candidate
GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?
Current atherosclerosis reports2022 Nov (month)PMID36044100doi:10.1007/s11883-022-01062-2via pubmed acronym asset candidate
Review article: role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes-what hepatologists need to know.
Alimentary pharmacology & therapeutics2022 Apr (month)PMID35266164doi:10.1111/apt.16794via pubmed acronym asset candidate
Development of Cagrilintide, a Long-Acting Amylin Analogue.
Journal of medicinal chemistry2021 Aug 12PMID34288673doi:10.1021/acs.jmedchem.1c00565via pubmed acronym asset candidate

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.