Pharmacological Class
Antidiabetic agents — SGLT2 (sodium-glucose cotransporter 2) inhibitors.
Mechanism of Action
- Inhibit SGLT2 in the proximal renal tubule, reducing reabsorption of filtered glucose.
- → Increase urinary glucose excretion, thereby lowering plasma glucose levels.
- Also promote natriuresis and osmotic diuresis, which reduce preload and afterload — beneficial in heart failure.
Common Agents & Brands
| Generic Name | Brand Name |
|---|---|
| Dapagliflozin | Farxiga |
| Empagliflozin | Jardiance |
| Canagliflozin | Invokana |
| Ertugliflozin | Steglatro |
Indications
- Type 2 Diabetes Mellitus (T2DM) – as monotherapy or add-on.
- Heart Failure (HFrEF & HFpEF) – even without diabetes.
- Chronic Kidney Disease (CKD) – slows progression and reduces risk of hospitalization.
Key Clinical Benefits
- ↓ HbA1c (~0.5–1%)
- ↓ Body weight and blood pressure
- ↓ Risk of hospitalization for heart failure
- ↓ Progression of diabetic kidney disease
- ↓ Cardiovascular and all-cause mortality (esp. empagliflozin, dapagliflozin)
Pharmacokinetics
- Oral once daily, with or without food
- Renal elimination: dose adjustments or avoidance in low eGFR (varies by agent)
Contraindications
- Type 1 diabetes (↑ DKA risk)
- Severe renal impairment (eGFR <30 mL/min/1.73m² for most)
- Hypersensitivity
Adverse Effects
| System | Adverse Effect | Pharmacist Notes |
|---|---|---|
| Genitourinary | Genital mycotic infections, UTI | Counsel on hygiene |
| Metabolic | Euglycemic diabetic ketoacidosis (DKA) | Rare but serious |
| Renal | Initial eGFR drop, dehydration | Monitor renal function |
| Cardiovascular | Hypotension, esp. in elderly/diuretic use | Monitor BP |
| Bone | Fracture risk (Canagliflozin) | Use cautiously |
| Limb | Amputation risk (Canagliflozin) | Caution in PAD |
Monitoring Parameters
- HbA1c, fasting glucose
- eGFR (baseline and periodically)
- Serum electrolytes (Na⁺, K⁺)
- Volume status and BP
- Signs of infection (genital/urinary)
- Ketones in suspected DKA
Clinical Pearls for Pharmacists
- Hold during acute illness, surgery, or dehydration (risk of DKA).
- May continue in non-diabetic HF or CKD patients if eGFR adequate.
- Combination therapy: often used with metformin, GLP-1 agonists, or insulin.
- Reassure patients about transient increase in urination and genital irritation.
- Educate on sick day management.
Synonyms
SGLT2 Inhibitors