SGLT2 inhibitors are glucose-lowering agents that block sodium-glucose cotransporter-2 in the proximal tubule.

They were developed for diabetes but are now foundational therapies in:

• Heart Failure • Chronic Kidney Disease • Type 2 Diabetes

These drugs provide cardiovascular and renal protection independent of glucose lowering.

Location:

• Proximal convoluted tubule

Action:

• Block SGLT2 transporter • Decrease glucose reabsorption • Increase urinary glucose excretion • Increase mild natriuresis

Net Effects:

• Lower blood glucose • Mild diuresis • Reduce intraglomerular pressure • Improve cardiac energetics • Reduce heart failure hospitalization

• Dapagliflozin • Empagliflozin • Sotagliflozin

All share similar mechanisms.

# Indications

• Improve glycemic control • Reduce cardiovascular events • Promote weight loss

Indicated for:

• HFrEF • HFpEF

Benefits:

• Reduce hospitalization • Reduce cardiovascular mortality • Effective regardless of diabetes status

→ Heart Failure Module

These are one of the Four Pillars in HFrEF.

• Reduce progression of CKD • Lower albuminuria • Slow decline in GFR

Renal benefit independent of diabetes.

# Adverse Effects

Common:

• Genital mycotic infections • Polyuria • Volume depletion • Hypotension

Serious:

• Euglycemic DKA (rare) • Fournier gangrene (rare)

# Contraindications

• Type 1 diabetes (DKA risk) • Severe volume depletion • Advanced renal failure (varies by drug)

# SGLT2 vs Other Diabetes Agents

Unlike:

• GLP-1 Receptor Agonists

SGLT2 inhibitors:

• Provide strong heart failure benefit • Provide renal protection • Cause mild diuresis

GLP-1 agents:

• Stronger weight loss • Greater atherosclerotic benefit

# Clinical Pearls

✔ Work in proximal tubule ✔ Mild diuretic effect ✔ Reduce HF hospitalization ✔ Reduce CKD progression ✔ Benefit independent of diabetes status ✔ Part of HFrEF Four Pillars

Related:

→ Heart Failure Module → Cardiovascular Modules → Endocrine Pharmacology