Elpida

• Type 1 Diabetes Mellitus (T1DM):
  Adjunct to insulin therapy to improve glycemic control in adults with inadequate control despite optimal insulin therapy.
• Type 2 Diabetes Mellitus (T2DM):
  Used as adjunct to diet and exercise to improve glycemic control in adults with T2DM, especially when metformin is inadequate or not tolerated.
• Off-label/Investigational Uses:
  Under study for potential cardiovascular and renal benefits beyond glycemic control.

• Adults:
  Initial dose: 200 mg orally once daily, administered in the morning.
  May be increased to 400 mg once daily after 2 to 4 weeks if tolerated and additional glycemic control is needed.
• Administration:
  Tablets should be taken orally with or without food at the same time each day.
• Dose Adjustments:
• No dose adjustment required for mild or moderate renal impairment.
• Not recommended in severe renal impairment or end-stage renal disease.
• Use with caution in hepatic impairment; data limited.
• Pediatrics:
  Safety and efficacy not established.
• Elderly:
  Use caution; monitor renal function regularly.

Sotagliflozin is a dual inhibitor of sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2). By inhibiting SGLT2 in the renal proximal tubules, it reduces glucose reabsorption, increasing urinary glucose excretion, thereby lowering plasma glucose. Inhibition of SGLT1 in the gastrointestinal tract delays intestinal glucose absorption, reducing postprandial glucose spikes. This dual inhibition improves overall glycemic control and may contribute to additional cardiovascular benefits.

• Absorption: Rapid oral absorption; peak plasma concentration approximately 1 to 3 hours post-dose.
• Bioavailability: Approximately 75%.
• Distribution: Highly plasma protein bound (~99.5%).
• Metabolism: Primarily metabolized by UGT1A9 and UGT2B7 to inactive metabolites.
• Half-life: Approximately 13 hours, supporting once-daily dosing.
• Elimination: Mainly excreted in feces (~70%) and urine (~20%) as metabolites.

• Pregnancy: No established FDA category; animal studies show adverse effects; use only if benefits justify risks.
• Lactation: Unknown if excreted in human milk; breastfeeding not recommended during treatment.

• Primary Therapeutic Class: Antidiabetic agent
• Subclass: Dual SGLT1 and SGLT2 inhibitor

• Known hypersensitivity to sotagliflozin or any excipients
• Severe renal impairment or end-stage renal disease
• Diabetic ketoacidosis (DKA) or history of DKA
• Type 1 diabetes patients not on insulin therapy

• Risk of diabetic ketoacidosis even with normal blood glucose levels; educate patients on symptoms.
• Increased risk of genital mycotic infections and urinary tract infections.
• Monitor volume status; risk of hypotension and dehydration, especially in elderly or those on diuretics.
• Use cautiously in patients with hepatic impairment.
• Monitor renal function before and during therapy.
• Avoid use in severe renal impairment due to reduced efficacy and increased adverse events.
• Potential risk of hypoglycemia when used with insulin or insulin secretagogues.

Common:

• Genital fungal infections (e.g., vulvovaginal candidiasis, balanitis)
• Urinary tract infections
• Diarrhea
• Nausea
• Hypoglycemia (especially when combined with insulin)
• Increased urination

Serious but rare:

• Diabetic ketoacidosis (including euglycemic DKA)
• Volume depletion and hypotension
• Acute kidney injury
• Fournier’s gangrene (necrotizing fasciitis of the perineum)

• Insulin and Insulin Secretagogues: Increased risk of hypoglycemia; dose adjustment may be needed.
• Diuretics: Increased risk of volume depletion and hypotension.
• Rifampin and other UGT inducers: May reduce sotagliflozin plasma concentrations, reducing efficacy.
• No significant CYP450 involvement; minimal interactions expected via this pathway.

• Approval supported by large cardiovascular outcomes trials showing potential benefits in reducing heart failure hospitalizations in diabetes patients.
• FDA and EMA emphasize monitoring for ketoacidosis signs and proper patient education.
• Updated recommendations encourage caution in patients with moderate renal impairment.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container until use.
• No refrigeration or special reconstitution required.