SGLT2 Inhibitors: Complete List and Overview
Currently Available SGLT2 Inhibitors
Four SGLT2 inhibitors are FDA-approved and commercially available for treating type 2 diabetes in adults:
- Empagliflozin (Jardiance) - approved for glycemic control and cardiovascular risk reduction 1
- Canagliflozin - demonstrated cardiovascular benefits in the CANVAS trials 2
- Dapagliflozin (Farxiga) - approved for diabetes, heart failure, and chronic kidney disease 3, 4
- Ertugliflozin - the most recently approved agent in this class 5, 6
Additional SGLT2 inhibitors available in certain countries include:
- Ipragliflozin - available in Japan 7
- Luseogliflozin - available in Japan 7
- Tofogliflozin - available in Japan 7
Mechanism of Action
All SGLT2 inhibitors work by blocking sodium-glucose cotransporter-2 proteins in the proximal renal tubules, which reduces glucose reabsorption and increases urinary glucose excretion. 5, 4 This mechanism operates independently of insulin secretion or action, making these medications effective regardless of diabetes duration 5.
Standard Dosing Across the Class
- Empagliflozin: 10 mg or 25 mg once daily 2, 8
- Canagliflozin: 100 mg or 300 mg once daily 2, 8
- Dapagliflozin: 10 mg once daily (fixed dose, no titration needed) 2, 8, 3
- Ertugliflozin: Standard dosing per FDA approval 5
Clinical Benefits Beyond Glycemic Control
SGLT2 inhibitors provide HbA1c reduction of 0.5-1.0%, promote weight loss of 1.5-3.5 kg, and lower systolic blood pressure by 3-5 mmHg. 5, 9 More importantly, empagliflozin and canagliflozin reduce major adverse cardiovascular events (MACE) and heart failure hospitalization 2, with empagliflozin specifically reducing cardiovascular death by 38% and all-cause mortality by 32% 2.
Renal Function Requirements
Assess eGFR before initiating any SGLT2 inhibitor:
- Empagliflozin should not be initiated if eGFR <45 mL/min/1.73 m² 8
- Canagliflozin and dapagliflozin can be initiated down to eGFR 25-30 mL/min/1.73 m² for cardiovascular and renal protection 8, 10
- Glucose-lowering efficacy decreases with declining renal function, but cardiovascular and renal benefits persist at lower eGFR levels 10
Safety Profile
Common adverse events across the class include:
- Genital mycotic infections (approximately 6% vs 1% placebo) 8, 4, 9
- Urinary tract infections 4, 6
- Euglycemic diabetic ketoacidosis (rare but serious) 8, 6, 9
- Volume depletion and hypotension 8, 9
The hypoglycemia risk is low when used as monotherapy, but increases when combined with insulin or sulfonylureas. 5, 4