Sotagliflozin for Diabetic Kidney Disease

(SUGARNSALT Trial)

Recruiting at 20 trial locations

Overseen By Emily Collins

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

Trial Summary

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.

What data supports the effectiveness of the drug Sotagliflozin for diabetic kidney disease?

Research shows that Sotagliflozin, a drug that helps control blood sugar by blocking certain proteins, has been effective in improving kidney function in people with type 2 diabetes and chronic kidney disease. It has also been shown to improve blood sugar control in type 1 diabetes, although it carries a risk of diabetic ketoacidosis (a serious diabetes complication). ^{1 2 3 4 5}

Is sotagliflozin safe for humans?

Sotagliflozin is generally well tolerated in humans, but it carries a risk of diabetic ketoacidosis (a serious condition where the body produces high levels of blood acids called ketones). This risk has been noted in studies for both type 1 and type 2 diabetes. ^{1 3 4 5 6}

How is the drug sotagliflozin unique for diabetic kidney disease?

Sotagliflozin is unique because it is a dual inhibitor of sodium-glucose co-transporters 1 and 2, which means it works by both delaying glucose absorption in the gut and reducing glucose reabsorption in the kidneys. This dual action can help manage blood sugar levels and potentially benefit kidney function in patients with diabetes. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

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

Eligibility Criteria

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

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

I am currently using anti-TNF alpha medications.

I have had a severe diabetic complication in the last 3 months or more than once in the last year.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Sotagliflozin: First Global Approval. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease. [2023]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. [2022]