Sotagliflozin

Sotagliflozin is an inhibitor of SGLT2 and SGLT1. Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium which may influence several physiological functions such as lowering both pre-and afterload of the heart and downregulating sympathetic activity.

• INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors INPEFA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ( 1 ) or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors ( 1 )ICD-10: E11.9, I50.9, N18.9

• INPEFA is contraindicated in patients with a history of serious hypersensitivity reaction to INPEFA. History of serious hypersensitivity reaction to INPEFA.contraindicated

Correct volume status before starting INPEFA at 200 mg daily and titrate to 400 mg as tolerated. ( 2.2 ) In patients with decompensated heart failure, begin dosing when patients are hemodynamically stable. ( 2.1 ) Withhold INPEFA at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. ( 2.3 ) 2.1 Prior to Initiation of INPEFA Assess volume status and, if necessary, correct volume depletion prior to initiation of INPEFA [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.5 , 8.6 )] . Assess renal function prior to initiation of INPEFA and then as clinically indicated [see Warnings and Precautions ( 5.2 )] . For patients with decompensated heart failure, dosing may begin as soon as the patient is hemodynamically stable, including during hospitalization or urgent outpatient treatment or immediately upon discharge. 2.2 Recommended Dosage The recommended starting dose of INPEFA is 200 mg orally once daily not more than one hour before the first meal of the day. Up-titrate after at least 2 weeks to 400 mg orally once daily as tolerated [see Clinical Studies ( 14 )] . Down-titrate to 200 mg as necessary [see Adverse Reactions ( 6.1 ), Warnings and Precautions ( 5 ) and Use in Specific Populations ( 8.6 )]. Swallow tablets whole. Do not cut, crush, or chew tablets. If a dose of INPEFA is missed by more than 6 hours, take the next dose as prescribed the next day.

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INPEFA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. ( 5.1 ) Volume Depletion: Before initiating, correct volume status. Monitor for signs and symptoms of hypotension during therapy. ( 5.2 ) Urosepsis and Pyelonephritis: Monitor for signs and symptoms during therapy and treat promptly. ( 5.3 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Lower dose of insulin or insulin secretagogue may be required. ( 5.4 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Monitor for pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. Discontinue INPEFA and treat urgently. ( 5.5 ) Genital Mycotic Infections : Monitor and treat as appropriate. ( 5.6 ) 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, INPEFA significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate.

The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions ( 5.1 )] Volume Depletion [see Warnings and Precautions ( 5.2 )] Urosepsis and Pyelonephritis [see Warnings and Precautions ( 5.3 )] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions ( 5.4 )] Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see Warnings and Precautions ( 5.5 )] Genital Mycotic Infections [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (incidence ≥ 5%) are urinary tract infection, volume depletion, diarrhea, and hypoglycemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lexicon at 1-855-330-2573 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the phase 3 (SOLOIST [see Clinical Studies ( 14.1 )] and SCORED [see Clinical Studies ( 14.2 )] ) placebo-controlled trials, 5,896 subjects received INPEFA. In the SOLOIST study, 336 patients (56%) reached the 400 mg dose. In the SCORED study, 3,934 patients (74%) reached the 400 mg dose.

Pregnancy : Advise females of the potential risk to a fetus especially during the second and third trimesters. ( 8.1 ) Lactation : INPEFA is not recommended when breastfeeding. ( 8.2 ) Geriatrics : Higher incidence of adverse reactions related to volume depletion. ( 5.2 , 8.5 ) Renal Impairment : Higher incidence of adverse reactions related to volume depletion. ( 5.2 , 8.6 ) 8.1 Pregnancy Risk Summary Based on animal data showing renal effects, INPEFA is not recommended during the second and third trimesters of pregnancy. Available data with INPEFA in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated heart failure in pregnancy [see Clinical Considerations ] . In rats, renal changes were observed when sotagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Exposure approximately 5 times the clinical exposure at the maximum recommended human dose (MRHD) of 400 mg once daily caused increased kidney weights and renal pelvis and tubule dilatations that were partially reversible [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

Plasma C max and AUC of sotagliflozin increased in a dose-proportional manner in the therapeutic dose range of 200 mg to 400 mg once daily. Accumulation of sotagliflozin was observed with an approximate 50-100% increase in both C max and area under the concentration-time curve from 0 to 24 hours (AUC 0-24h ) at steady state verses the first day of dosing.

There were no confirmed reports of symptomatic overdose with sotagliflozin during the clinical development program of INPEFA. In the event of an overdose with INPEFA, contact the Poison Control Center. Employ the usual supportive measures as dictated by the patient's clinical status. The removal of sotagliflozin by hemodialysis has not been studied.

• May 26, 2023NDANDA216203Lexicon Pharms Inc

1. 1Dizziness5210%
2. 2Diarrhoea479.1%
3. 3Death356.7%
4. 4Therapy Interrupted336.4%
5. 5Dyspnoea265.0%
6. 6Off Label Use254.8%
7. 7Headache234.4%
8. 8Product Use Issue234.4%
9. 9Urinary Tract Infection234.4%
10. 10Nausea193.7%
11. 11Fungal Infection173.3%
12. 12Drug Ineffective142.7%
13. 13Fatigue142.7%
14. 14Malaise142.7%
15. 15Vomiting142.7%

The 10 most recently updated of 55 ClinicalTrials.gov registrations naming Sotagliflozin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Precision T1D Platform - New Therapies for Cardio-Renal Complications
  Not yet recruiting · Phase 2 · Interventional · 57 enrolled · Oregon Health and Science University
  NCT07594145updated 2026-05-20
• A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy
  Recruiting · Phase 3 · Interventional · 500 enrolled · Lexicon Pharmaceuticals
  NCT06481891updated 2026-05-18
• Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
  Not yet recruiting · Phase 4 · Interventional · 64 enrolled · Baylor Research Institute
  NCT07547878updated 2026-05-08
• Sotagliflozin as Prevention of Anthracycline-Related Cardiotoxicity
  Not yet recruiting · Phase 2 · Interventional · 60 enrolled · Icahn School of Medicine at Mount Sinai
  NCT07572175updated 2026-05-07
• Antithrombotic Activities of Sotagliflozin vs. Empagliflozin
  Completed · Phase 4 · Interventional · 17 enrolled · Icahn School of Medicine at Mount Sinai
  NCT06618976updated 2026-04-30
• Sotagliflozin in Patients With Heart Failure Symptoms and Type 1 Diabetes
  Recruiting · Phase 2 · Interventional · 320 enrolled · University of Dundee
  NCT06435156updated 2026-04-06
• Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease
  Recruiting · Phase 3 · Interventional · 150 enrolled · Alessandro Doria
  NCT06217302updated 2026-03-24
• Ketone Monitoring Approaches for Diabetic Ketoacidosis Risk Mitigation in People With T1D on Adjunctive SGLT-2 Inhibitors
  Not yet recruiting · Phase 2 · Interventional · 75 enrolled · AdventHealth Translational Research Institute
  NCT07421518updated 2026-02-19
• Sodium Glucose Co-transporter (SGLT) Inhibitors in Nonobstructive Hypertrophic Cardiomyopathy
  Recruiting · Early phase 1 · Interventional · 26 enrolled · University of Pennsylvania
  NCT06433050updated 2026-02-11
• Reducing Risk of Diabetic Ketoacidosis in Type 1 Diabetes and Kidney Disease Using Continuous Ketone Monitoring
  Not yet recruiting · Phase 2 · Interventional · 80 enrolled · HealthPartners Institute
  NCT07325201updated 2026-02-04

Frequently asked questions

How does Sotagliflozin work?

Sotagliflozin is an inhibitor of SGLT2 and SGLT1. Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium which may influence several physiological functions such as lowering both pre-and afterload of the heart and downregulating sympathetic activity.

What is Sotagliflozin used for?

According to FDA labeling, Sotagliflozin carries indications including: INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors INPEFA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ( 1 ) or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors ( 1 ). This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sotagliflozin?

Sotagliflozin is classified as Sodium-glucose co-transporter 2 (SGLT2) inhibitors, Sodium-Glucose Cotransporter 2 Inhibitor, P-Glycoprotein Inhibitors, Sodium-Glucose Transporter 2 Inhibitors.

What are the brand names for Sotagliflozin?

Sotagliflozin is marketed under brand names including Inpefa.

What are the contraindications for Sotagliflozin?

Sotagliflozin labeling lists contraindications including: INPEFA is contraindicated in patients with a history of serious hypersensitivity reaction to INPEFA. History of serious hypersensitivity reaction to INPEFA.. Always consult the full prescribing information and a clinician.