Diabetic NephropathiesPhase 3SUGARNSALTNCT06217302
Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease
A Phase 3 study testing Sotagliflozin in people with Diabetic Nephropathies and Kidney Failure, Chronic, run by Alessandro Doria at 19 sites in 2 countries.
Trial summary
Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetic Nephropathies, Kidney Failure, Chronic, Diabetes Mellitus Type 1
- What is being tested?
- Sotagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 31 Oct 2024to May 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type1 diabetes (T1D) continuously treated with insulin within one year from diagnosis.
- Duration of T1D ≥ 8 years;
- eGFR based on serum creatinine and cystatin c (2021 serum creatinine-cystatin C CKD-EPI equation) between 20 and 60 ml/min/1.73 m2 at screening (with the option of a second eGFR measurement within 4 weeks from the first one if the eGFR was in the range of >60 to ≤65 or ≥16 to <20 ml/min/1.73 m2);
- a. First morning void urinary albumin creatinine ratio (UACR) ≥200 mg/g at Screening or on repeat measurement within 4 weeks from the first one, or b. First morning void urinary UACR ≥100 mg/g at Screening or on repeat measurement within 4 weeks and at least one uACR >=30 in the previous 2 years while treated with RASB at a stable dose;
- HbA1c at screening <10% (with the option of a second HbA1c measurement within 4 weeks from the first one if the HbA1c was ≤10.2%);
- Receiving standard of care, including renin angiotensin system blockers (RASB) at a clinically appropriate dose, unless contraindicated or not tolerated.
- Willing and able to comply with schedule of events and protocol requirements, including written informed consent, and willing to wear a continuous glucose monitoring (CGM) device for the entire duration of the study.
- a. Blood pressure ≤155/95 mmHg at screening, or b. BP ≤155/95 mmHg at the end of the run-in period, or c. consistent BP ≤155/95 mmHg on home monitoring during the run-in period, as determined by study site investigator, despite BP values >155/95 mmHg in clinic.
Who cannot join
- Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease;
- Use of automated insulin delivery devices that are not approved by health regulatory agencies, or used in ways that do not align with manufacturer recommendations;
- Use of any SGLT inhibitor in the previous 2 months;
- Use of dual medication RASB therapy (spironolactone, eplerenone, finerenone are allowed in combination with RASB therapy);
- Use of GLP-1 receptor agonists and other non-insulin glucose-lowering agents if not on stable dose for > 2 months at screening (patients can be rescreened after being on stable dose for > 2 months);
- Use of anti tumor necrosis factor (TNF) alpha biologic medications at screening;
Show all 23Show fewer
- Known allergies, hypersensitivity, or intolerance to SOTA;
- History of ≥3 severe hypoglycemic events (requiring third-party assistance for correction) within 3 months of screening;
- History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar state within 3 months of screening OR >1 episode of DKA or non-ketotic hyperosmolar state within 12 months of screening;
- Blood beta-hydroxybutyrate (BHB) >0.6 mmol/L for >2 hours on >2 occasions during the Run-in period;
- Inadequate beta hydroxybutyrate (BHB) testing (<50% of the prescribed measurements) during Run-in;
- History of primary renal glycosuria;
- History of biopsy-proven non-diabetic chronic kidney disease (CKD);
- History of kidney transplant or currently on chronic dialysis;
- Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites or hepatic encephalopathy), and/or known diagnosis of cirrhosis based on liver biopsy, imaging, or elastography, and/or aspartate aminotransferase (AST) or alanine transaminase (ALT) at screening >2 times upper limit of normal, and/or total bilirubin at screening >1.3 times upper limit of normal).
- History of severe acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection or severely immunocompromised status;
- Cancer treatment (excluding non-melanoma skin cancer treated by excision, carcinoma in situ of the cervix or uterus, ductal breast cancer in situ, resected non-metastatic breast or prostate cancer) within one year of screening.
- Illicit drug abuse within 6 months of screening;
- Heavy alcohol use (for men, 5 drinks or more on any day or 15 drinks or more per week; for women, 4 drinks or more on any day or 8 drinks or more per week);
- Participation in another interventional clinical research study within 30 days of screening;
- Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial;
- Presence of a clinically significant medical history, physical examination, or laboratory finding that may interfere with any aspect of study conduct or interpretation of results;
- Any condition that may render the patient unable to comply with study requirements and/or complete the study.
Trial locations and contacts
19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 2 countries
United States13 sites, 13 recruiting
- Recruiting
Barbara Davis Center / University of Colorado Denver
Aurora, Colorado, 80045
Matthew Klein, BA, Matthew.P.Klein@cuanschutz.edu
Scott Maclean, Scott.2.maclean@cuanschutz.edu
- Recruiting
Joslin Diabetes Center
Boston, Massachusetts, 02215
Christine Mendonca, 617-334-2257, christine.mendonca@joslin.harvard.edu
Alessandro Doria, MD PhD MPH
- Recruiting
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Marianna Colucci, marianna.colucci@northwestern.edu
Christina Coventry, MSN RN, christina.coventry@northwestern.edu
- Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Kelly Paulus, PAULUSK2@ccf.org
Maya Boyd, BOYDA5@ccf.org
- Recruiting
University of Texas Southwestern
Dallas, Texas, 75390
Lina Gonzalez Duarte, Lina.GonzalezDuarte@UTSouthwestern.edu
Jovana Valdez, Jovana.Valdez@UTSouthwestern.edu
- Recruiting
AdventHealth
Orlando, Florida, 32803
Ivette Moreno, Ivette.Moreno@AdventHealth.com
Tina Thethi
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Alyssa Carlson, carlsaly@ohsu.edu
Krista Metas, RN, metas@ohsu.edu
- Recruiting
University of Washington
Seattle, Washington, 98105
Anjali Kumari, anjalikr@uw.edu
Bri Hihara, bhihara@uw.edu
- Recruiting
Providence Sacred Heart Medical Center
Spokane, Washington, 99204
Nicole Maser, Nicole.maser@providence.org
Katherine R. Tuttle, MD
- Recruiting
Washington University
St Louis, Missouri, 63110
Heather Schaefer, hschaefer@wustl.edu
Janet McGill, MD
- Recruiting
Stanford University Medical Center
Stanford, California, 94305
Grace Deala, gdeala@stanford.edu
Arati Nagarkar, MD, arati.nagarkar@stanford.edu
- Recruiting
SUNY Upstate Medical University
Syracuse, New York, 13210
Jane Bulger, MS, CCRC, 315-464-9008, BulgerJ@upstate.edu
Susan Bzdick, bzdicks@upstate.edu
- Recruiting
Albert Einstein College of Medicine / Montefiore Medical Center
The Bronx, New York, 10461
Cynthia Rivera, BS, cynthia.rivera@einsteinmed.edu
Sally Duran, BA, sally.duran@einsteinmed.edu
Canada6 sites, 6 recruiting
- Recruiting
Unversity of Calgary
Calgary, Alberta, T2T 5C7
Jenny Schulz, jennifer.schulz@ucalgary.ca
Michelle Smith, RN, mahunter@ucalgary.ca
- Recruiting
Alberta Diabetes Institute
Edmonton, Alberta, T6G 2E1
Dominique Forrest, dforres1@ualberta.ca
Jyoti Singh, jyoti1@ualberta.ca
- Recruiting
Institut de Recherches Cliniques de Montréal
Montreal, Quebec, H2W 1R7
Roxane St Amand, roxane.st-amand@ircm.qc.ca
Marie Raffray, marie.Raffray@ircm.qc.ca
- Recruiting
LMC Diabetes and Endocrinology
Toronto, Ontario, M4G 3E8
Lydia Beaudette, Lydia.Beaudette@clinsurge.ca
Arlene Vinas, Arlene.Vinas@ElevateResearch.ca
- Recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2N2
Vesta Lai, RN, 416-586-4800 ext. 7625, Vesta.Lai@uhn.ca
Cheng Xu, 416-586-4800 ext. 7187, Cheng.Xu@uhn.ca
- Recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Paula Macleod, pmacleod@providencehealth.bc.ca
Adeera Levin, MD
About this study
Official title: Effectiveness and Safety of Sotagliflozin in Slowing Kidney Function Decline in Persons With Type 1 Diabetes and Moderate to Severe Diabetic Kidney Disease
Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline in patients with T1D and DKD.
Read the detailed description
Despite improvements in glycemia management and the use of renin-angiotensin system blockade (RASB), the overall incidence of ESKD incidence in the US T1D population is not decreasing. For patients with type 2 diabetes (T2D), powerful new drugs that can prevent or delay ESKD, sodium-glucose cotransporter-2 inhibitors (SGLT2i), are now available. Whether similar results can be achieved in T1D remains unknown because of the paucity of studies in this population, due to concerns about the 2- to 3-fold increase in risk of diabetic ketoacidosis (DKA) associated with SGLT2i therapy in T1D. One of the few T1D studies conducted to date (inTandem, a sotagliflozin [SOTA] trial), showed that implementation of an enhanced DKA risk monitoring and mitigation strategy can reduce DKA incidence to <1%/year in subjects on 200 mg/day of this dual SGLT1 and SGLT2 inhibitor. The goals of the present study are to evaluate the renal effectiveness of SGLT2i in T1D and to better understand the benefit/risk ratio of SOTA in T1D persons with moderate to advanced diabetic kidney disease (DKD) - two goals that are warranted and critical given the high risk of death and ESKD in this population. The study, carried out by the Preventing Early Renal Loss (PERL) and the Canadian Institute of Health Research (CIHR)-funded SUGARNSALT (S\&S) consortia, is a multi-center, double-blind, placebo-controlled, parallel-group randomized clinical trial in 150 patients with T1D and moderate to advanced diabetic kidney disease (estimated glomerular filtration rate [eGFR] 20-60 ml/min/1.73 m2 and ACR>200 mg/g). After a 2-month run-in period, during which diabetes care is standardized and education on monitoring and minimizing DKA implemented, eligible study subjects are randomized in a 1:1 ratio to receive placebo or once daily 200 mg SOTA for 3 years followed by a 2-month wash-out period. The eGFR at the end of the wash-out adjusted by its baseline value will be used as the primary outcome on which SOTA efficacy on DKD progression will be evaluated. An intensive DKA risk mitigation plan will be implemented based on the inTandem enhanced protocol as well as on the STICH (Stop SGLT2i, Insulin administration, Carbohydrate intake, Hydration) and STOP-DKA protocols. Cornerstones of this plan will be enhanced participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body (beta-hydroxybutyrate [BHB]) self-monitoring. If successful, the present study will provide efficacy and safety data that could be used to seek FDA and Health Canada approval of SOTA for a T1D DKD indication. Based on the available data in T1D, it can be conservatively postulated that SOTA may reduce eGFR loss by 2 ml/min/1.73 m2 per year. Depending on the baseline eGFR, this would translate to a 5-10 year delay of ESKD. The reduction in morbidity and mortality resulting from the prevention or delay of ESKD due to the use of SOTA would have a major impact on the lives of T1D patients with significant DKD as well as on society at large, substantially reducing the human and financial costs associated with this condition.
- Being tested
- Sotagliflozin, Placebo
- Keywords
- Diabetic Nephropathies, Kidney Failure, Chronic, Type 1 diabetes, Heart failure, Cardiovascular disease, Glomerular filtration rate, SGLT2 inhibitors, Diabetic kidney disease
- Medical subject headings
- Diabetic Nephropathies, Kidney Failure, Chronic, Diabetes Mellitus, Type 1, Heart Failure, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotagliflozinDrug
Also called INPEFA
Oral sotagliflozin (200 mg per day)
PlaceboDrug
Inactive tablets identical to sotagliflozin tablets
| Study group | Role | What they receive |
|---|---|---|
| Sotagliflozin | Active comparator | Oral sotagliflozin at a dose of 200 mg (one tablet) per day for three years followed by a 2-month wash-out period. Receives: Drug: Sotagliflozin |
| Placebo | Placebo comparator | Oral tablets similar to sotagliflozin tablets but containing no active drug (one tablet per day for three years followed by a 2-month wash-out period). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
eGFR at the end of the wash-out period following the treatment period
eGFR at the end of the 8-week drug washout period following the 3-year treatment period, estimated from Central Lab serum creatinine and cystatin C using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and adjusted by its baseline value. Baseline and end-of-washout eGFRs will be considered as the average of two eGFR values taken on two separate days before randomization (V2 and V4) and after the washout (V18 and V19), respectively.
Measured: End of the 2-month wash-out period following the 3-year treatment period (weeks 162 and 164)
Secondary outcomes (1)
Time to ≥40% eGFR decline from baseline, kidney failure , or death from renal causes
Time from randomization to 1. sustained ≥40% eGFR decline (based on eGFR estimated from serum creatinine and cystatin C using the 2021 CKD-EPI equation) confirmed after 30 days; 2. kidney failure, defined by eGFR ≤10ml/min/ 1.73m2 confirmed after 30 days or occurring within 30 days prior to death, or initiation of maintenance kidney replacement therapy; or 3. death from kidney-related causes. If an eGFR value meeting the above criteria is observed at the last study visit or immediately before a participant is lost to follow-up or withdraws from the study, no confirmation of this value will be necessary.
Measured: Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start31 Oct 2024
- Primary completionDec 2028 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alessandro Doria
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Kidney Foundation of Canada, The Cleveland Clinic, University of Michigan, University of Colorado, Denver, Northwestern University, Washington University School of Medicine, State University of New York - Upstate Medical University, Providence Medical Research Center, Stanford University, Montefiore Medical Center, University of Toronto, University Health Network, Toronto, University of Calgary, University of Alberta, University of British Columbia, Institut de Recherches Cliniques de Montreal, LMC Diabetes & Endocrinology Ltd., Joslin Diabetes Center, Lexicon Pharmaceuticals, DexCom, Inc., University of Washington, Breakthrough T1D, AdventHealth
- Responsible party
- Sponsor-investigator, Alessandro Doria, Joslin Diabetes Center
- Investigators
- Alessandro Doria, MD PhD MPH, Principal investigator, Joslin Diabetes CenterMichael Mauer, MD, Principal investigator, University of MinnesotaDavid Cherney, MD PhD, Principal investigator, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217302
- Sponsor's protocol ID
- STUDY00000249
- Acronym
- SUGARNSALT
- Status last verified
- Mar 2026
- First submitted
- 9 Jan 2024
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van Raalte DH, Bjornstad P, Persson F, Powell DR, de Cassia Castro R, Wang PS, Liu M, Heerspink HJL, Cherney D. The Impact of Sotagliflozin on Renal Function, Albuminuria, Blood Pressure, and Hematocrit in Adults With Type 1 Diabetes. Diabetes Care. 2019 Oct;42(10):1921-1929. doi: 10.2337/dc19-0937. Epub 2019 Aug 1.
PubMed 31371432Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Diaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021 Jan 14;384(2):129-139. doi: 10.1056/NEJMoa2030186. Epub 2020 Nov 16.
PubMed 33200891Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16.
PubMed 33200892Markham A, Keam SJ. Sotagliflozin: First Global Approval. Drugs. 2019 Jun;79(9):1023-1029. doi: 10.1007/s40265-019-01146-5.
PubMed 31172412Nardone M, Kugathasan L, Sridhar VS, Dutta P, Campbell DJT, Layton AT, Perkins BA, Barbour S, Lam TKT, Levin A, Lovblom LE, Mucsi I, Rabasa-Lhoret R, Rac VE, Senior P, Sigal RJ, Stanimirovic A, Persson F, Stougaard EB, Doria A, Cherney DZI. Modeling Cardiorenal Protection with Sodium-Glucose Cotransporter 2 Inhibition in Type 1 Diabetes: An Analysis of DEPICT-1 and DEPICT-2. Clin J Am Soc Nephrol. 2025 Apr 1;20(4):529-538. doi: 10.2215/CJN.0000000641. Epub 2025 Feb 7.
PubMed 39918875
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness and Safety of Sotagliflozin in Slowing Kidney Function Decline in Persons With Type 1 Diabetes and Moderate to Severe Diabetic Kidney Disease
- ClinicalTrials.gov ID
- NCT06217302
- Acronym / sponsor ID
- SUGARNSALT / STUDY00000249
- Keywords
- Diabetic Nephropathies, Kidney Failure, Chronic, Type 1 diabetes, Heart failure, Cardiovascular disease, Glomerular filtration rate, SGLT2 inhibitors, Diabetic kidney disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Alessandro DoriaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Kidney Foundation of Canada, The Cleveland Clinic, University of Michigan, University of Colorado, Denver, Northwestern University, Washington University School of Medicine, State University of New York - Upstate Medical University, Providence Medical Research Center, Stanford University, Montefiore Medical Center, University of Toronto, University Health Network, Toronto, University of Calgary, University of Alberta, University of British Columbia, Institut de Recherches Cliniques de Montreal, LMC Diabetes & Endocrinology Ltd., Joslin Diabetes Center, Lexicon Pharmaceuticals, DexCom, Inc., University of Washington, Breakthrough T1D, AdventHealth
- Study start
- 31 Oct 2024 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline in patients with T1D and DKD.
Detailed description
Despite improvements in glycemia management and the use of renin-angiotensin system blockade (RASB), the overall incidence of ESKD incidence in the US T1D population is not decreasing. For patients with type 2 diabetes (T2D), powerful new drugs that can prevent or delay ESKD, sodium-glucose cotransporter-2 inhibitors (SGLT2i), are now available. Whether similar results can be achieved in T1D remains unknown because of the paucity of studies in this population, due to concerns about the 2- to 3-fold increase in risk of diabetic ketoacidosis (DKA) associated with SGLT2i therapy in T1D. One of the few T1D studies conducted to date (inTandem, a sotagliflozin [SOTA] trial), showed that implementation of an enhanced DKA risk monitoring and mitigation strategy can reduce DKA incidence to <1%/year in subjects on 200 mg/day of this dual SGLT1 and SGLT2 inhibitor. The goals of the present study are to evaluate the renal effectiveness of SGLT2i in T1D and to better understand the benefit/risk ratio of SOTA in T1D persons with moderate to advanced diabetic kidney disease (DKD) - two goals that are warranted and critical given the high risk of death and ESKD in this population. The study, carried out by the Preventing Early Renal Loss (PERL) and the Canadian Institute of Health Research (CIHR)-funded SUGARNSALT (S\&S) consortia, is a multi-center, double-blind, placebo-controlled, parallel-group randomized clinical trial in 150 patients with T1D and moderate to advanced diabetic kidney disease (estimated glomerular filtration rate [eGFR] 20-60 ml/min/1.73 m2 and ACR>200 mg/g). After a 2-month run-in period, during which diabetes care is standardized and education on monitoring and minimizing DKA implemented, eligible study subjects are randomized in a 1:1 ratio to receive placebo or once daily 200 mg SOTA for 3 years followed by a 2-month wash-out period. The eGFR at the end of the wash-out adjusted by its baseline value will be used as the primary outcome on which SOTA efficacy on DKD progression will be evaluated. An intensive DKA risk mitigation plan will be implemented based on the inTandem enhanced protocol as well as on the STICH (Stop SGLT2i, Insulin administration, Carbohydrate intake, Hydration) and STOP-DKA protocols. Cornerstones of this plan will be enhanced participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body (beta-hydroxybutyrate [BHB]) self-monitoring. If successful, the present study will provide efficacy and safety data that could be used to seek FDA and Health Canada approval of SOTA for a T1D DKD indication. Based on the available data in T1D, it can be conservatively postulated that SOTA may reduce eGFR loss by 2 ml/min/1.73 m2 per year. Depending on the baseline eGFR, this would translate to a 5-10 year delay of ESKD. The reduction in morbidity and mortality resulting from the prevention or delay of ESKD due to the use of SOTA would have a major impact on the lives of T1D patients with significant DKD as well as on society at large, substantially reducing the human and financial costs associated with this condition.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sotagliflozin | Active comparator | Drug: SotagliflozinOral sotagliflozin at a dose of 200 mg (one tablet) per day for three years followed by a 2-month wash-out period. |
| Placebo | Placebo comparator | Drug: PlaceboOral tablets similar to sotagliflozin tablets but containing no active drug (one tablet per day for three years followed by a 2-month wash-out period). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Type1 diabetes (T1D) continuously treated with insulin within one year from diagnosis.
- Duration of T1D ≥ 8 years;
- eGFR based on serum creatinine and cystatin c (2021 serum creatinine-cystatin C CKD-EPI equation) between 20 and 60 ml/min/1.73 m2 at screening (with the option of a second eGFR measurement within 4 weeks from the first one if the eGFR was in the range of >60 to ≤65 or ≥16 to <20 ml/min/1.73 m2);
- a. First morning void urinary albumin creatinine ratio (UACR) ≥200 mg/g at Screening or on repeat measurement within 4 weeks from the first one, or b. First morning void urinary UACR ≥100 mg/g at Screening or on repeat measurement within 4 weeks and at least one uACR >=30 in the previous 2 years while treated with RASB at a stable dose;
- HbA1c at screening <10% (with the option of a second HbA1c measurement within 4 weeks from the first one if the HbA1c was ≤10.2%);
Key exclusion criteria (23 listed)
- Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease;
- Use of automated insulin delivery devices that are not approved by health regulatory agencies, or used in ways that do not align with manufacturer recommendations;
- Use of any SGLT inhibitor in the previous 2 months;
- Use of dual medication RASB therapy (spironolactone, eplerenone, finerenone are allowed in combination with RASB therapy);
- Use of GLP-1 receptor agonists and other non-insulin glucose-lowering agents if not on stable dose for > 2 months at screening (patients can be rescreened after being on stable dose for > 2 months);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotagliflozinAlso: INPEFAOral sotagliflozin (200 mg per day) | Drug | Sotagliflozin |
| PlaceboInactive tablets identical to sotagliflozin tablets | Drug | Placebo |
Primary outcome
eGFR at the end of the wash-out period following the treatment period
Time frame: End of the 2-month wash-out period following the 3-year treatment period (weeks 162 and 164)
eGFR at the end of the 8-week drug washout period following the 3-year treatment period, estimated from Central Lab serum creatinine and cystatin C using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and adjusted by its baseline value. Baseline and end-of-washout eGFRs will be considered as the average of two eGFR values taken on two separate days before randomization (V2 and V4) and after the washout (V18 and V19), respectively.
1 secondary outcome
Time to ≥40% eGFR decline from baseline, kidney failure , or death from renal causes
Time frame: Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Background: PubMed 31371432van Raalte DH, Bjornstad P, Persson F, Powell DR, de Cassia Castro R, Wang PS, Liu M, Heerspink HJL, Cherney D. The Impact of Sotagliflozin on Renal Function, Albuminuria, Blood Pressure, and Hematocrit in Adults With Type 1 Diabetes. Diabetes Care. 2019 Oct;42(10):1921-1929. doi: 10.2337/dc19-0937. Epub 2019 Aug 1.
- Background: PubMed 33200891Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Diaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021 Jan 14;384(2):129-139. doi: 10.1056/NEJMoa2030186. Epub 2020 Nov 16.
- Background: PubMed 33200892Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16.
- Background: PubMed 31172412Markham A, Keam SJ. Sotagliflozin: First Global Approval. Drugs. 2019 Jun;79(9):1023-1029. doi: 10.1007/s40265-019-01146-5.
- Derived from this study: PubMed 39918875Nardone M, Kugathasan L, Sridhar VS, Dutta P, Campbell DJT, Layton AT, Perkins BA, Barbour S, Lam TKT, Levin A, Lovblom LE, Mucsi I, Rabasa-Lhoret R, Rac VE, Senior P, Sigal RJ, Stanimirovic A, Persson F, Stougaard EB, Doria A, Cherney DZI. Modeling Cardiorenal Protection with Sodium-Glucose Cotransporter 2 Inhibition in Type 1 Diabetes: An Analysis of DEPICT-1 and DEPICT-2. Clin J Am Soc Nephrol. 2025 Apr 1;20(4):529-538. doi: 10.2215/CJN.0000000641. Epub 2025 Feb 7.
- Individual participant dataSharing planned: No
Related trials for Diabetic Nephropathies
Active, not recruitingPhase 2
A Study on the Safety and Clinical Efficacy of Guominkang in the Treatment of Diabetic Kidney Disease
Diabetic Kidney Disease (DKD), Type 2 Diabetes
RecruitingObservational study
Study of High Density Lipoprotein Function in Type 1 Diabetic Patients With Nephropathy
Type 1 Diabetes
RecruitingPhase 2
Study to Assess the Effects of ALN-ANG3 in Adult Participants With Diabetic Kidney Disease
Diabetic Kidney Disease (DKD)
Not yet recruitingPhase 2
Mitigating DKA in Type 1 Diabetes for Safe Use of SGLT Inhibitors Using Dual Continuous Ketone and Glucose Monitoring.
Type 1 Diabetes Mellitus, Chronic Kidney Disease (CKD) With Diabetes Mellitus (DM)
Not yet recruitingObservational study
Impact of AI-Based Breath Ammonia Kidney Function Results on Clinical Pharmacist Medication Recommendations
Diabetes Mellitus, Type 2, Diabetic Nephropathies
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alessandro Doria, MD PhD MPH principal investigator
Joslin Diabetes Center
Michael Mauer, MD principal investigator
University of Minnesota
David Cherney, MD PhD principal investigator
University of Toronto
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sotagliflozin in people with Diabetic Nephropathies and Kidney Failure, Chronic, run by Alessandro Doria at 19 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christine Mendonca (617-334-2257, christine.mendonca@joslin.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
eGFR at the end of the wash-out period following the treatment period (time frame: End of the 2-month wash-out period following the 3-year treatment period (weeks 162 and 164)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06217302, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.