Sotagliflozin

Sotagliflozin is a dual SGLT2 and SGLT1 inhibitor used for heart failure and diabetes.

Unlike other SGLT2 inhibitors, sotagliflozin also inhibits SGLT1 in the intestine.

→ SGLT2 Inhibitors Overview

SGLT2 inhibition (kidney):

• Blocks glucose reabsorption in proximal tubule • Causes glucosuria • Causes mild natriuresis • Reduces intraglomerular pressure

SGLT1 inhibition (intestine):

• Reduces postprandial glucose absorption • Blunts post-meal glucose spikes

Net Effects:

• ↓ Blood glucose • Mild osmotic diuresis • ↓ Preload • ↓ Blood pressure • Cardiorenal protection

Indicated for:

• HFrEF • HFpEF • Worsening heart failure

Benefits:

• ↓ HF hospitalization • ↓ Cardiovascular events • Works with or without diabetes

→ Heart Failure Module

• Improves glycemic control • Blunts postprandial glucose rise

SOLOIST-WHF:

• Reduced cardiovascular death and HF events • Studied in patients recently hospitalized for worsening HF

SCORED:

• Reduced cardiovascular events in diabetic patients with CKD

Common:

• Genital mycotic infections • Diarrhea (more common due to SGLT1 inhibition) • Volume depletion • Hypotension

Serious (rare):

• Euglycemic DKA • Fournier gangrene

• Type 1 diabetes • Severe dehydration • Advanced renal impairment (indication-dependent)

Hold during:

• Acute illness • Surgery • Prolonged fasting

Dapagliflozin and Empagliflozin:

• • Pure SGLT2 inhibitors
• • No intestinal SGLT1 inhibition

Sotagliflozin:

• • Dual SGLT1 + SGLT2 inhibition
• • Greater postprandial glucose reduction
• • More GI side effects

All provide:

• • Heart failure benefit
• • Renal protection

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✔ Dual SGLT1 and SGLT2 inhibitor ✔ Reduces HF hospitalization ✔ Useful after recent HF hospitalization ✔ Causes more GI side effects than other gliflozins ✔ Benefit independent of diabetes status

Related:

→ Heart Failure Module → SGLT2 Inhibitors Overview → Cardiovascular Modules