Sotagliflozin for Platelet Activation Control

Overseen By Amanda Prieur

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Michigan

Must not be taking: NSAIDs, Anticoagulants, SSRIs, SNRIs

Disqualifiers: Type I diabetes, Alcohol abuse, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking NSAIDs (like Ibuprofen or Naproxen) at least 7 days before the study and anticoagulants 10 days before. You also cannot participate if you are currently taking SSRIs, SNRIs, lithium, or omeprazole/esomeprazole.

What data supports the effectiveness of the drug Sotagliflozin for controlling platelet activation?

Research shows that drugs similar to Sotagliflozin, like other SGLT2 inhibitors, can reduce platelet activation and oxidative stress, which are important in preventing blood clots. Additionally, Sotagliflozin has been effective in managing heart failure and diabetes, which suggests it may have benefits in controlling platelet activation as well. ^{1 2 3 4 5}

Is sotagliflozin generally safe for humans?

Sotagliflozin has been studied for safety in people with type 1 and type 2 diabetes, as well as heart failure. It generally shows acceptable safety, with no increased risk for serious conditions like diabetic ketoacidosis or urinary tract infections, though it may cause mild diarrhea. ^{2 5 6 7 8}

How is the drug sotagliflozin unique for controlling platelet activation?

Sotagliflozin is unique because it is a dual inhibitor of sodium-glucose cotransporters (SGLT) 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 is different from other treatments that typically target only one of these pathways. ^{2 5 7 9 10}

What is the purpose of this trial?

This study will identify the potential benefits of regulating platelet activation with sotagliflozin compared to other FDA-approved drugs known to limit platelet activation.

Research Team

Michael Holinstat, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for individuals who can undergo platelet function tests to study the effects of different antiplatelet drugs. Specific inclusion and exclusion criteria details are not provided, so participants should consult with the trial organizers for eligibility.

Exclusion Criteria

Subjects with a history of alcohol abuse, pancreatitis or pancreatic surgery, or subjects taking a ketogenic diet

Subjects with a creatinine greater than or equal to 1.5 mg/dl will be excluded

Students under the direct supervision of Dr. Michael Holinstat

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of sotagliflozin, aspirin, clopidogrel, or apixaban in randomized order

2 weeks

1 visit (in-person) every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotagliflozin

Trial Overview The study is testing the antiplatelet effects of Sotagliflozin (SOTA) compared to three FDA-approved drugs: Aspirin, Clopidogrel, and Eliquis. Each drug will be followed by three others in a random order to assess their impact on platelet activation.

Participant Groups

Group I: Platelet function in healthy subjects administered sotagliflozin vs. antiplatelet agents Experimental Treatment 4 Interventions

Platelet responsiveness will be assessed in the blood from subjects administered sotagliflozin, aspirin, clopidogrel, or apixaban in randomized order given as a single drug administration.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

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

Findings from Research

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]

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 significantly improves glycemic control in adults with type 1 diabetes, reducing HbA1c levels and insulin requirements while also enhancing time in the target glucose range, based on a meta-analysis of six trials involving 3,238 participants over 4 to 52 weeks.

While sotagliflozin reduces the incidence of hypoglycemia, it does increase the risk of diabetic ketoacidosis and other side effects, indicating that careful patient management and insulin dose adjustments are necessary to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials. Musso, G., Gambino, R., Cassader, M., 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]

In a 29-day study involving 33 patients with type 1 diabetes, sotagliflozin significantly reduced bolus insulin doses by 32.1% and improved glycemic control, as indicated by lower mean daily glucose levels and a decrease in HbA1c by 0.55%.

Sotagliflozin also increased the percentage of time patients spent in the target glucose range (70-180 mg/dL) to 68.2% and decreased time spent in the hyperglycemic range (>180 mg/dL) to 25%, all while promoting weight loss without increasing the risk of hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Sands, AT., Zambrowicz, BP., Rosenstock, J., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study. [2023]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sotagliflozin in treating diabetes type 1. [2018]

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

The Effect of Dapagliflozin on Platelet Function Testing Profiles in Diabetic Patients: The EDGE Pilot Study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Sotagliflozin for patients with type 2 diabetes: A systematic review and meta-analysis. [2022]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. [2018]

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

Sotagliflozin: First Global Approval. [2020]

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

Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. [2022]