Sotagliflozin for Diabetic Kidney Disease

(SUGARNSALT Trial)

Recruiting at 22 trial locations

Overseen By Alexis Puthussery

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alessandro Doria

Must be taking: Insulin, RASB

Must not be taking: SGLT inhibitors, GLP-1 agonists

Disqualifiers: Type 2 diabetes, DKA history, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 156 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called sotagliflozin to determine if it can prevent kidney damage in people with type 1 diabetes and kidney disease. Researchers aim to find out if this drug can slow kidney function loss without causing serious complications like diabetic ketoacidosis, a condition where blood becomes too acidic. Participants will take either the drug or a placebo (a pill with no active ingredients) daily for three years. This trial may suit those who have had type 1 diabetes for at least 8 years and are experiencing kidney issues affecting their daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used any SGLT inhibitors in the past 2 months or be on certain other medications like dual RASB therapy or GLP-1 receptor agonists unless you've been on a stable dose for at least 3 months.

Is there any evidence suggesting that sotagliflozin is likely to be safe for humans?

Research has shown that sotagliflozin is generally safe for people with diabetes and chronic kidney disease. In one study, 23.4% of participants taking sotagliflozin experienced serious side effects, compared to 25.2% of those taking a placebo (a pill with no active drug), indicating similar safety levels between the drug and placebo.

For people with type 1 diabetes, sotagliflozin did not significantly increase the risk of diabetic ketoacidosis (DKA), a serious diabetes complication. Although a few cases of DKA occurred, a special prevention plan helped keep this risk low.

Overall, the treatment appears well-tolerated, but monitoring for any risks remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic kidney disease?

Sotagliflozin is unique because it targets the kidneys in a way that many standard treatments for diabetic kidney disease do not. While most treatments focus on controlling blood sugar levels or managing blood pressure, sotagliflozin works by inhibiting certain proteins in the kidneys, specifically SGLT1 and SGLT2. This dual inhibition can help reduce the progression of kidney damage by lowering glucose reabsorption and improving kidney function. Researchers are excited about sotagliflozin because this approach not only addresses the root cause but also offers a potentially more effective way to protect kidney health in people with diabetes.

What evidence suggests that sotagliflozin might be an effective treatment for diabetic kidney disease?

Research has shown that sotagliflozin, which participants in this trial may receive, can help people with diabetes and chronic kidney disease by reducing the risk of kidney deterioration. Studies have found that this drug can delay the need for dialysis and kidney transplants over ten years, thereby offering longer kidney protection. Sotagliflozin also benefits heart health in people with type 2 diabetes and chronic kidney disease. Although concerns exist about diabetic ketoacidosis (DKA), a condition where harmful substances build up in the blood, improved prevention plans have successfully lowered this risk. These findings suggest that sotagliflozin might also help people with type 1 diabetes by slowing kidney damage and reducing the need for more intensive treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

David Cherney

Principal Investigator

University of Toronto

Alessandro Doria, MD PhD MPH

Principal Investigator

Joslin Diabetes Center

Michael Mauer, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people with Type 1 Diabetes who also have moderate to advanced diabetic kidney disease. Participants should be willing to follow a strict program to prevent diabetic ketoacidosis, including education and regular monitoring. Those at risk of DKA or unable to adhere to the prevention plan are excluded.

Inclusion Criteria

HbA1c <10% at screening

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

I am on standard treatment for my condition, including RASB, unless I cannot tolerate it.

Exclusion Criteria

I am currently using anti-TNF alpha medications.

Any condition that may render the patient unable to comply with study requirements and/or complete the study

Inadequate beta hydroxybutyrate (BHB) testing (<50% of the prescribed measurements) during Run-in

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Diabetes care is standardized and education on monitoring and minimizing DKA is implemented

8 weeks

Treatment

Participants receive either sotagliflozin or placebo for 3 years with continuous glucose monitoring and DKA risk mitigation

156 weeks

Regular visits for monitoring (weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140, 156)

Wash-out

Participants undergo a 2-month period without treatment to assess the wash-out effects

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sotagliflozin

Trial Overview The study tests if Sotagliflozin can slow down kidney function decline in Type 1 Diabetes patients with kidney disease. Half will receive Sotagliflozin; the other half a placebo, randomly assigned. The trial includes a DKA prevention program and spans over three years plus two months without treatment.

How Is the Trial Designed?

Group I: Sotagliflozin Active Control 1 Intervention

Oral sotagliflozin at a dose of 200 mg (one tablet) per day for three years followed by a 2-month wash-out period.

Group II: Placebo Placebo Group 1 Intervention

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).

Sotagliflozin is already approved in European Union, United States for the following indications:

Approved in European Union as Zynquista for:

• Type 1 diabetes mellitus

Approved in United States as Inpefa for:

• Heart failure
• Type 2 diabetes mellitus
• Chronic kidney disease

Who Is Running the Clinical Trial?

Alessandro Doria

Lead Sponsor

Trials

3

Recruited

720+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

DexCom, Inc.

Industry Sponsor

Trials

151

Recruited

35,700+

Kevin Sayer

DexCom, Inc.

Chief Executive Officer since 2015

Bachelor’s and Master’s degrees in Accounting and Information Systems from Brigham Young University

Dr. Shelly Lane

DexCom, Inc.

Chief Medical Officer since 2023

MD from University of California, San Diego

Institut de Recherches Cliniques de Montreal

Collaborator

Trials

72

Recruited

10,300+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Lexicon Pharmaceuticals

Industry Sponsor

Trials

67

Recruited

24,400+

Dr. Mike Exton

Lexicon Pharmaceuticals

Chief Executive Officer

PhD in Neuroscience from the University of Newcastle and PhD in Immunology from the University of Essen, Germany

Dr. Craig Granowitz

Lexicon Pharmaceuticals

Chief Medical Officer since 2021

MD

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Published Research Related to This Trial

Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, significantly improved glycemic control, reduced body weight, and lowered insulin requirements in adults with type 1 diabetes over 24 weeks, with benefits maintained for up to 52 weeks.

The drug is generally well tolerated and does not increase the risk of hypoglycemia, although it does carry a risk of diabetic ketoacidosis, making it a valuable adjunct to insulin therapy for overweight or obese patients with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: A Review in Type 1 Diabetes. Deeks, ED.[2020]

Sotagliflozin, a dual SGLT 1 and 2 inhibitor, has been shown to significantly reduce HbA1c levels in patients with type 1 diabetes when used alongside optimized insulin therapy, indicating its efficacy as a treatment option.

Despite its benefits, sotagliflozin is associated with a higher risk of diabetic ketoacidosis compared to placebo, which raised safety concerns during the FDA review process, leading to its approval only in the EU for specific patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: First Global Approval. Markham, A., Keam, SJ.[2020]

Canagliflozin, an SGLT-2 inhibitor introduced for type 2 diabetes, shows potential for type 1 diabetes treatment due to its insulin-independent mechanism of action.

However, it carries serious risks, including severe metabolic acidosis and euglycemic diabetic ketoacidosis, which require immediate recognition and treatment to prevent life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. Gelaye, A., Haidar, A., Kassab, C., et al.[2022]

Sotagliflozin, a new medication for diabetes, was found to be safe for renal function, showing no significant adverse effects on kidney health in a review of 14 studies involving 17,574 participants, including those with existing renal impairment.

The drug did not significantly change urinary albumin excretion or the risk of composite renal events, indicating that while it is safe, more research is needed to fully understand its effectiveness in preventing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Bantounou, MA., Sardellis, P., Thuemmler, R., et al.[2023]

In a 52-week study involving 277 adults with type 2 diabetes and stage 4 chronic kidney disease, sotagliflozin 400 mg did not show statistically significant reductions in HbA1c compared to placebo after 26 weeks, although there was a notable reduction at 52 weeks.

The safety profile of sotagliflozin was generally consistent with previous studies, with a lower percentage of serious cardiovascular adverse events in the sotagliflozin groups compared to placebo, indicating it may be a safer option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment. Cherney, DZI., Ferrannini, E., Umpierrez, GE., et al.[2022]

In a phase 3 trial involving 787 adults with type 2 diabetes and stage 3 chronic kidney disease, sotagliflozin 400 mg significantly reduced HbA1c levels compared to placebo after 26 weeks, while the 200 mg dose did not show significant efficacy.

Both doses of sotagliflozin led to reductions in urine albumin-creatinine ratio (UACR) in patients with at least A2 albuminuria, indicating potential renal benefits, although these changes were not sustained at 52 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease. Cherney, DZI., Ferrannini, E., Umpierrez, GE., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2030186

Sotagliflozin in Patients with Diabetes and Chronic Kidney ... The percentage of patients with a serious adverse event was 23.4% in the sotagliflozin group and 25.2% in the placebo group (Table S9). Adverse ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33200891/

Sotagliflozin in Patients with Diabetes and Chronic Kidney ... Conclusions: In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06217302

NCT06217302 | Sotagliflozin to Slow Kidney Function ... 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 ...

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2025.31.7.641

Cost-effectiveness analysis model for sotagliflozin ... Sotagliflozin slowed rates of dialysis and transplant over a 10-year time frame, decreased mortality, and was found to provide good value for ...

5. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2020/11/11/22/02/SCORED

Effect of Sotagliflozin on Cardiovascular and Renal Events ... The results of this trial indicate that sotagliflozin has salutary effects on CV outcomes among patients with T2DM and CKD.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39485484/

Efficacy and Safety of Sotagliflozin in Patients with Type 1 ... In participants with type 1 diabetes and CKD, sotagliflozin did not significantly increase the risk of DKA, however, there were a small number ...

7. inpefahcp.com inpefahcp.com/

Heart Failure Treatment | INPEFA® (sotagliflozin) HCP The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 ...

8. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/s/NCT06217302.html

Sotagliflozin to Slow Kidney Function Decline in Persons With ... 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 ...