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.
Kidney transplantation improves survival and quality of life for patients with kidney failure. However, treatment options to protect the heart and the kidney in transplant recipients are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs which not only lower blood sugar, but also lower blood pressure in the kidney's individual filtering units and protect kidney function in the long term. It is unclear if the protective mechanisms of these drugs also occur in people with a kidney transplant. Several smaller studies have shown that SGLT2 inhibitors or GLP-1RA used alone are safe in people with kidney transplants. No studies have yet to look at the combined use of SGLT2 inhibitors and GLP-1RA in kidney transplant recipients (KTR). The purpose of the HALLMARK study is to determine the mechanisms and safety of the combination use of semaglutide, a GLP-1RA, and dapagliflozin, a SGLT2 inhibitor. To investigate this, 20 kidney transplant recipients with and without diabetes will be treated with both semaglutide or dapagliflozin for 12 weeks followed by a combination of semaglutide and dapagliflozin for 12 weeks. The study will measure salt and water removal as well as the effect on blood pressure, kidney function, heart function, liver stiffness as well as the safety of these agents.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Semaglutide subcutaneous once weekly for 12 weeks.
Dapagliflozin oral once daily for 12 weeks.
Toronto General Hospital
Toronto, Ontario, Canada
RECRUITINGProximal tubular natriuresis with combination therapy
Measured by fractional excretion of sodium
Time frame: From baseline to combination therapy end (24 weeks)
Proximal tubular natriuresis with monotherapy
Measured by fractional excretion of sodium
Time frame: From baseline to monotherapy end (12 weeks)
Measured Glomerular Filtration Rate
GFR, based on plasma iohexol clearance
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Estimated Glomerular Filtration Rate
GFR, based on serum creatinine
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration
Using ELISA
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Urinary albumin excretion
From 24-hour urine collection
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Arterial stiffness
Measured using a Sphygmocor device
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Liver stiffness
Using transient elastography
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Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Diastolic function
Using 2D echocardiography
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in percentage of glycated hemoglobin (HbA1c)
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in concentration of urine glucose excretion
Urinary analysis will be performed to quantify the amount of glucose excretion.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in body composition (percent body mass, body fat, and muscle mass)
Bioimpedence measurements will be taken to study the effects of intervention on body composition.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in body weight
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: the incidence of acute kidney injury.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: the incidence of hypotension
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of hyperkalemia
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of urinary and mycotic infections.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The number of ketoacidosis events.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of amputations.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of pancreatitis or biliary complications
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The number of allergic reaction events.
Time frame: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]