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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how sotagliflozin, an SGLT2 inhibitor, might aid people with heart failure who have a strong heart pump, known as preserved ejection fraction. Researchers aim to determine if the drug offers benefits beyond blood sugar control, particularly for the heart and kidneys. Participants will take either sotagliflozin or a placebo (a pill resembling the medicine but without active ingredients) for six months. This trial suits individuals diagnosed with heart failure, who do not have diabetes, and maintain a consistently strong heart pump. As a Phase 4 trial, sotagliflozin has already received FDA approval and proven effective, and this research seeks to understand how it benefits more patients.

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 is the safety track record for sotagliflozin?

Research has shown that sotagliflozin has been studied in people with diabetes and heart problems. In the SOLOIST-WHF trial, researchers tested it on over 1,200 patients with diabetes who had worsening heart failure. The results indicated that sotagliflozin was generally safe and well-tolerated. Although the study examined some side effects, the treatment overall helped without causing major problems.

Sotagliflozin is already approved for managing heart failure, indicating it has undergone extensive safety testing. While every treatment can have side effects, the approval suggests it is considered safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Sotagliflozin is unique because it works by inhibiting two proteins, SGLT1 and SGLT2, which play a role in heart failure. Most treatments for heart failure, like ACE inhibitors or beta-blockers, focus on managing symptoms and reducing heart workload. Sotagliflozin's dual action not only helps control blood sugar levels but also reduces the risk of heart-related complications, offering a potentially broader benefit. Researchers are excited because this could mean improved heart health and better overall outcomes for patients with heart failure.

What is the effectiveness track record for sotagliflozin in treating heart failure?

Research has shown that sotagliflozin can help reduce heart failure events. In the SOLOIST-WHF study, patients who took sotagliflozin experienced 33% fewer heart-related problems compared to those who did not take it, resulting in fewer complications from heart failure. The SCORED trial also found that sotagliflozin helped people with type 2 diabetes and chronic kidney disease experience fewer heart failure issues. In this trial, participants will receive either sotagliflozin or a placebo to further evaluate its effectiveness for heart failure patients, regardless of heart pump function. ^{1 3 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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 do not have diabetes, as shown by my blood tests and medical history.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38014844/

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic ... SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52- ...

2. jacc.org jacc.org/doi/10.1016/j.jacc.2024.06.036

Effects of Sotagliflozin on Health Status in Patients With ... Sotagliflozin was shown to improve clinical endpoints among patients recently hospitalized with WHF in the SOLOIST-WHF (Effect of Sotagliflozin ...

3. investors.lexpharma.com investors.lexpharma.com/news-releases/news-release-details/sotagliflozin-provides-consistent-relative-risk-reduction-heart

Release Details - Investor Relations | Lexicon Pharmaceuticals The primary endpoint was total cardiovascular (CV) death, hospitalization for HF, or urgent visit for HF. Additional endpoints included total ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2030183

Sotagliflozin in Patients with Diabetes and Recent ... Sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213858724003620

Effect of sotagliflozin on major adverse cardiovascular events 1, 2, 3, 4 In the SCORED trial, sotagliflozin treatment resulted in a reduction in heart failure-related outcomes in patients with type 2 diabetes, chronic ...

6. inpefahcp.com inpefahcp.com/

Heart Failure Treatment | INPEFA® (sotagliflozin) HCP INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR <60 mL/min/1.73 m2. The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06435156

NCT06435156 | Sotagliflozin in Patients With Heart Failure ... The second key trial was the Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure (SOLOIST-WHF) trial. In this trial 1,222 patients with ...

8. lexpharma.com lexpharma.com/products/inpefa

INPEFA ® (sotagliflozin) INPEFA (sotagliflozin) · INPEFA is 1 of 3 SGLT inhibitors currently indicated for heart failure · SOLOIST-WHF included 1,222 patients recently hospitalized for ...