Background: Sodium-glucose-cotransporter (SGLT) inhibition has been observed to reduce risk of cardiovascular events and kidney failure in persons with type 2 diabetes. People with type 1 diabetes also have increased risk of cardiovascular and kidney disease, and may benefit from SGLT-inhibition. The exact mechanism of how SGLT-inhibition benefits the kidneys are yet unknown. Change in renal hypoxia may be a factor.
Objective: The primary aim of this study is to assess the effects of 12 weeks SGLT-1 and 2 inhibition on renal oxygenation in persons with type 1 diabetes and chronic kidney disease.
Further aims are to study if renal oxygen consumption and response to SGLT-inhibition differs between people of African-Caribbean or Northern European decent.
Additionally effects on left ventricular ejection fraction, kidney function and biomarkers in blood and urine will be explored.
Method: 12 weeks treatment with oral sotagliflozin or matching placebo as intervention. Kidney oxygenation and perfusion parameters and left ventricular ejection fraction will be assessed by functional magnetic resonance imaging. Kidney function and biomarkers will be assessed according to local hospital laboratory guidelines.
Design: Randomized, double-blinded, placebo-controlled, cross over intervention study.
Study population: 69 persons with type 1 diabetes and diabetic kidney disease with albuminuria will be included, 39 at Steno Diabetes Center Copenhagen, 30 at King's College London.
Endpoints: Primary end-point: Change from 0 to 12 weeks in dynamic R2\*-weighted signal after treatment with sotagliflozin compared to placebo. Secondary endpoints: Change from 0 to 12 weeks with sotagliflozin compared with placebo on renal perfusion, renal artery flow, renal oxygen consumption, renal parenchymal triglyceride fraction, renal fibrosis, left ventricular ejection fraction, urinary albumin-creatinin ratio, ketone bodies, erythropoietin, pro brain natriuretic peptide, and plasma- and urine inflammation- and fibrosis biomarkers as well as difference after 12 weeks treatment in glomerular filtration rate.
Timeframe: Inclusion of patients from february 2024. Last visit september 2025. Presentation spring 2026, publication fall 2026.
Persons ≥ 18 years of age with a diagnosis of type 1 diabetes (age at onset <40 years; permanent insulin treatment initiated within 1 year of diagnosis)
Albuminuria: UACR > 100 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
estimated Glomerular Filtration Rate(eGFR) ≥25 and < 75 ml/min/1.73m2
Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
Non-diabetic kidney disease indicated by medical history and/or laboratory findings.
eGFR< 25 ml/min/1.73m2, dialysis or kidney transplantation.
Previous diabetic ketoacidosis, except at debut.
Dysregulated diabetes (HbA1c > 85 mmol/mol)
Crossover
Sotagliflozin
DrugSodium-glucose-co-transporter 1 and 2 inhibitor
Placebo
DrugPlacebo tablet
Change in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation
difference between change from 0 to 12 weeks after treatment with sotagliflozin compared to treatment with placebo
Change in renal perfusion (medullary and cortical)
Measured with MRI by arterial spin labelling in mL/g/min
Change in renal artery flow
Renal artery flow measured by using phase contrast (PC) MRI. It is measured in mL/min.
Change in renal oxygen consumption
Renal oxygen consumption measured by MRI with T2-relaxation-under-spin-tagging.
Change in renal parenchymal triglyceride fraction
Renal parenchymal triglyceride fraction is measured by MRI spectroscopy
Ethnicity
if African-Caribbean ethnicity is associated with any of the above secondary outcomes or baseline differences in cardio-renal disease markers/imaging measures
Click on the lead sponsor to view all of their trials.
Steno Diabetes Center Copenhagen
Lead sponsor
Juvenile Diabetes Research Foundation
Collaborator
King's College London
Collaborator
Glostrup University Hospital, Copenhagen
Collaborator
Guy's and St Thomas' NHS Foundation Trust
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
