Sotagliflozin for Heart Failure

Overseen By Juan J Badimon

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Juan Badimon

Must be taking: Heart failure medications

Must not be taking: Digoxin, Phenytoin, HIV meds, Rifampin

Disqualifiers: Diabetes, Recent ACS, Low GFR, others

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: Unknown

Duration: 6 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The clinical benefits of the dual Sodium-Glucose cotransporter (SGLT) 1 and 2-inhibition have recently been reported in two clinical trials. The SOLOIST reported the benefits of sotagliflozin in Type-2 Diabetes Mellitus (T2DM) patients hospitalized for worsening of Heart Failure (HF), while the SCORED involved T2DM patients with Chronic Kidney Disease (CKD). It is worth noting that not only did the event curves separate within the first week post-treatment, but the effects of sotagliflozin on HF-related outcomes were observed regardless of Left Ventricular Ejection Fraction (LVEF) values and did not seem to attenuate with increasing LVEF as seen with empagliflozin and sacubitril/valsartan. Despite the favorable outcomes, the mechanism(s) of action through which sotagliflozin exerts these benefits remains unclear. The present study aims to investigate the potential (non-glucose dependent) "cardio-renal" pleiotropic effects of sotagliflozin in a mechanistic, randomized, double blind, placebo-control trial in HF patients with preserved ejection fraction (HFpEF). Comparisons between treatment groups will be made using cardiac MRI, CPET, 6-MWT and KCCQ-12.

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 must not be on drugs that interact with sotagliflozin, such as digoxin, phenytoin, HIV medication, and rifampin. Also, you should not have been taking SGLT2 inhibitors for 3 months before joining the trial.

What data supports the effectiveness of the drug Sotagliflozin for heart failure?

Research shows that Sotagliflozin reduced the total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure by 33% in patients with type 2 diabetes and worsening heart failure. Additionally, it displayed moderate cardiovascular benefits and acceptable safety in patients with heart failure or cardiovascular risk factors. ^{1 2 3 4 5}

Is sotagliflozin safe for use in humans?

Sotagliflozin has been generally well tolerated in clinical trials for type 1 and type 2 diabetes, but it carries a risk of diabetic ketoacidosis (a serious diabetes complication) and mild diarrhea. It has shown acceptable safety in heart failure patients, with no increased risk for urinary tract infections. ^{1 2 3 5 6}

How is the drug sotagliflozin unique for heart failure treatment?

Sotagliflozin is unique because it is the first dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1 and SGLT2), which helps manage heart failure by reducing heart failure events and major cardiovascular events in patients with type 2 diabetes and heart failure. This dual action distinguishes it from other treatments that typically target only SGLT2. ^{1 2 3 5 7}

Research Team

Juan J Badimon

Principal Investigator

Icahn School of Medicine at Mount Sinai

Carlos G Santos-Gallego, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults over 18 with heart failure who have a normal ejection fraction (LVEF > 50%) and are not diabetic. They must be on stable heart failure medication, except diuretics which need to be stable for at least two weeks. Women able to have children must use effective birth control during the study.

Inclusion Criteria

My heart's pumping ability is normal.

I've been on a stable heart failure medication for at least 4 weeks, except for water pills which have been stable for 2 weeks.

I am 18 years or older and can walk on my own.

Exclusion Criteria

I have diabetes.

Your kidneys are not filtering blood well enough, with a rate of less than 25 ml per minute per 1.73 square meters of body surface area.

I have been taking SGLT2 inhibitors for at least 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily administration of sotagliflozin or placebo for 6 months

6 months

Monthly visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotagliflozin

Trial Overview The trial is testing Sotagliflozin, a drug that may help heart failure patients without affecting blood sugar levels. It's compared against a placebo in a double-blind setup where neither doctors nor patients know who gets the real medicine. Effects will be checked using heart scans and physical tests.

Participant Groups

Group I: Sotagliflozin Experimental Treatment 1 Intervention

Daily administration of sotagliflozin (2x200 mg, orally, once a day) for 6 months.

Group II: Placebo Placebo Group 1 Intervention

Daily administration of placebo (2 tablet identical in appearance and color to sotagliflozin tablets, orally, once a day) for 6 months.

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?

Juan Badimon

Lead Sponsor

Trials

2

Recruited

100+

Findings from Research

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]

Sotagliflozin, the first dual inhibitor of SGLT1 and SGLT2, has shown significant efficacy in reducing cardiovascular and heart failure events in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial with a hazard ratio of 0.67.

While sotagliflozin expands treatment options for heart failure, existing SGLT2 inhibitors like dapagliflozin and empagliflozin have more robust evidence supporting their use, particularly in heart failure and chronic kidney disease, indicating that further research is needed to clarify sotagliflozin's role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. Long, A., Salvo, M.[2023]

In the SOLOIST-WHF trial involving 1222 patients with type 2 diabetes and recent heart failure hospitalization, sotagliflozin significantly increased the days alive and out of the hospital (DAOH) by 3% compared to placebo, indicating its potential to improve patient outcomes.

Sotagliflozin reduced the rate of days dead by 29% (RR 0.71) rather than significantly decreasing hospitalizations, suggesting that its primary benefit lies in enhancing survival rather than just reducing hospital visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. Szarek, M., Bhatt, DL., Steg, PG., et al.[2021]

Sotagliflozin demonstrated significant cardiovascular benefits in type 2 diabetes patients with heart failure, showing a reduction in heart failure events and major adverse cardiovascular events compared to other treatments like dapagliflozin and empagliflozin, based on a meta-analysis of 11 studies involving 30,952 patients.

The safety profile of sotagliflozin was acceptable, with no increased risk of diabetic ketoacidosis or urinary tract infections, although it did present a mild risk of diarrhea compared to placebo, making it a viable option for managing T2DM in patients with heart failure or cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis. Li, J., Zhu, C., Liang, J., et al.[2023]

In a large retrospective cohort study involving over 55,000 patients with type 2 diabetes, canagliflozin was associated with a significantly lower risk of hospital admission for heart failure compared to DPP-4 inhibitors, GLP-1 receptor agonists, and sulfonylureas.

Canagliflozin showed similar risks for major cardiovascular events (like heart attacks and strokes) when compared to these other diabetes medications, indicating its safety profile in terms of cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. Patorno, E., Goldfine, AB., Schneeweiss, S., et al.[2022]

Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, was well tolerated in a Phase I study involving 24 healthy Chinese subjects, with no serious adverse events reported, indicating a favorable safety profile.

The drug demonstrated rapid absorption and significant increases in urinary glucose excretion, suggesting its efficacy in improving glycemic control, with dose-proportional systemic exposure observed at both 200 mg and 400 mg doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Sotagliflozin After Multiple Ascending Doses in Chinese Healthy Subjects. He, X., Gao, X., Xie, P., et al.[2022]

References

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

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

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

Sotagliflozin: First Global Approval. [2020]

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

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. [2023]

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

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. [2022]

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

Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Sotagliflozin After Multiple Ascending Doses in Chinese Healthy Subjects. [2022]