Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease

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. 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.

Conditions

• Diabetic Nephropathies
• Kidney Failure, Chronic
• Diabetes Mellitus Type 1
• Heart Failure

Interventions

DRUG

Sotagliflozin

Oral sotagliflozin (200 mg per day)

DRUG

Placebo

Inactive tablets identical to sotagliflozin tablets

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• The Kidney Foundation of Canada

  collaborator OTHER

• The Cleveland Clinic

  collaborator OTHER

• University of Michigan

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• Northwestern University

  collaborator OTHER

• Washington University School of Medicine

  collaborator OTHER

• State University of New York - Upstate Medical University

  collaborator OTHER

• Providence Medical Research Center

  collaborator OTHER

• Stanford University

  collaborator OTHER

• Montefiore Medical Center

  collaborator OTHER

• University of Toronto

  collaborator OTHER

• University Health Network, Toronto

  collaborator OTHER

• University of Calgary

  collaborator OTHER

• University of Alberta

  collaborator OTHER

• University of British Columbia

  collaborator OTHER

• Institut de Recherches Cliniques de Montreal

  collaborator OTHER

• LMC Diabetes & Endocrinology Ltd.

  collaborator OTHER

• Joslin Diabetes Center

  collaborator OTHER

• Lexicon Pharmaceuticals

  collaborator INDUSTRY

• DexCom, Inc.

  collaborator INDUSTRY

• University of Washington

  collaborator OTHER

• Breakthrough T1D

  collaborator OTHER

• AdventHealth

  collaborator OTHER

• Alessandro Doria

  lead OTHER

Principal Investigators

• Alessandro Doria, MD PhD MPH · Joslin Diabetes Center

• Michael Mauer, MD · University of Minnesota

• David Cherney, MD PhD · University of Toronto

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-10-31

Primary Completion

2028-12-31

Completion

2029-05-31

FDA Drug

Yes

Countries

• United States
• Canada

Study Locations