Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia

• Sotagliflozin (Drug), also known as Inpefa (TM): Sodium-glucose-co-transporter 1 and 2 inhibitor
• Placebo (Drug): Placebo tablet

Primary outcomes

• Change in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation [0 to 12 weeks in both treatment arms, last measure 30 weeks after randomization.]: difference between change from 0 to 12 weeks after treatment with sotagliflozin compared to treatment with placebo

Secondary outcomes

• Change in renal perfusion (medullary and cortical) [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Measured with MRI by arterial spin labelling in mL/g/min
• Change in renal artery flow [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Renal artery flow measured by using phase contrast (PC) MRI. It is measured in mL/min.
• Change in renal oxygen consumption [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Renal oxygen consumption measured by MRI with T2-relaxation-under-spin-tagging.
• Change in renal parenchymal triglyceride fraction [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Renal parenchymal triglyceride fraction is measured by MRI spectroscopy
• Change in renal fibrosis [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Renal fibrosis is measured by MRI-derived apparent diffusion coefficient
• Change in left ventricular ejection fraction [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]: Left ventricular ejection fraction is assessed by MRI
• Change in albuminuria [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]: Urinary albumin-creatinine ratio (UACR) - morning void spot urine samples collected at home by participants.
• Change in levels of ketone bodies [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]: Capillary blood ketones, possibly measured by continous ketone monitoring device
• Change in plasma and urine inflammation- and fibrosis biomarkers [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]: Measured from blood and urine samples using a commercially available panel from the company Olink. Includes 92 biomarkers.
• Change in endogenous erythropoietin [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]: Analysis on blood samples at regional hospital laboratory.
• Change in pro brain natriuretic peptide [From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]: Analysis on blood samples at regional hospital laboratory.
• Difference in Kidney Function after 12 weeks treatment with sotagliflozin vs placebo [From 12 to 30 weeks after randomization]: Glomerular filtration rate. At Steno Diabetes Center Copenhagen this will be measured by plasma clearance of Tc-99m diethylene-triamine-pentaacetate.

Other outcomes

• Ethnicity [From baseline to 30 weeks.]: if African-Caribbean ethnicity is associated with any of the above secondary outcomes or baseline differences in cardio-renal disease markers/imaging measures

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. 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)
2. Albuminuria: UACR > 100 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
3. estimated Glomerular Filtration Rate(eGFR) ≥25 and < 75 ml/min/1.73m2
4. Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
5. Able to understand the written participant information and give informed consent

Exclusion Criteria:

1. Non-diabetic kidney disease indicated by medical history and/or laboratory findings.
2. eGFR< 25 ml/min/1.73m2, dialysis or kidney transplantation.
3. Previous diabetic ketoacidosis, except at debut.
4. Dysregulated diabetes (HbA1c > 85 mmol/mol)
5. Decreased awareness or unawareness
6. Pregnancy, lactating or with a wish of pregnancy within the next year
7. Low carbohydrate diet
8. Receiving therapy with an SGLT inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT inhibitor.
9. New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment
10. Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
11. The receipt of any investigational product 90 days prior to this trial
12. Unable to participate in study procedures
13. Any clinically significant disorder, except for conditions associated with type 1 diabetes, which in the Investigators opinion could interfere with the results of the trial
14. Participation in another intervention study
15. Exclusion criteria for MRI: known claustrophobia, known chronic lung disease, surgery within past 6 weeks or having foreign bodies of metal in the body (e.g. pacemaker, metal plates, metal screws)
16. Recurrent urogenital infections.