SGLT2 Inhibitor Medications for Type 2 Diabetes
The four FDA-approved SGLT2 inhibitors available in the United States are canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, all of which can serve as alternatives to metformin for adults with type 2 diabetes. 1, 2, 3
Available SGLT2 Inhibitor Medications
The SGLT2 inhibitor class includes the following specific agents:
- Canagliflozin (Invokana®): Available in 100 mg and 300 mg doses, with maximum approved daily dose of 300 mg 1, 3
- Dapagliflozin (Farxiga®): Available in 5 mg and 10 mg doses, with maximum approved daily dose of 10 mg 1, 2
- Empagliflozin (Jardiance®): Available in 10 mg and 25 mg doses, with maximum approved daily dose of 25 mg 1, 4
- Ertugliflozin (Steglatro®): Available in 5 mg and 15 mg doses, with maximum approved daily dose of 15 mg 1
Mechanism of Action
All SGLT2 inhibitors work through the same insulin-independent mechanism by blocking sodium-glucose cotransporter-2 in the proximal renal tubule, which reduces renal glucose reabsorption and increases urinary glucose excretion by approximately 70 grams per day. 5, 6, 7 This mechanism provides complementary therapy when combined with other antidiabetic agents and carries a low intrinsic risk of hypoglycemia when used alone or with metformin. 5
Clinical Indications for SGLT2 Inhibitors
For patients with heart failure (reduced or preserved ejection fraction): An SGLT2 inhibitor is recommended for both glycemic management and prevention of heart failure hospitalizations, irrespective of A1C level. 1
For patients with chronic kidney disease (eGFR 20-60 mL/min/1.73 m²): An SGLT2 inhibitor should be used for both glycemic management (irrespective of A1C) and for slowing progression of CKD and reduction in cardiovascular events. 1
For patients with established cardiovascular disease: SGLT2 inhibitors with demonstrated cardiovascular benefit (empagliflozin, canagliflozin, dapagliflozin) are recommended as part of the glucose-lowering regimen independent of A1C and independent of metformin use. 1, 8
Renal Function Considerations
The glycemic benefits of SGLT2 inhibitors are reduced at eGFR <45 mL/min/1.73 m², but cardiovascular and renal protective benefits persist even when glucose-lowering efficacy is minimal. 1, 9 SGLT2 inhibitors can be initiated in patients with eGFR ≥20 mL/min/1.73 m² and should be continued for cardiorenal protection even as eGFR declines below thresholds where glucose-lowering is minimal. 1, 9
Comparative Efficacy
All four SGLT2 inhibitors demonstrate similar glycemic efficacy, typically reducing HbA1c by approximately 0.7-1.0% when added to metformin. 1 The choice among specific agents should be guided by cardiovascular outcomes trial data, with empagliflozin, canagliflozin, and dapagliflozin having the strongest evidence for cardiovascular and renal benefits. 1, 8
Common Pitfalls to Avoid
Do not discontinue SGLT2 inhibitors solely because glucose-lowering efficacy has declined with reduced eGFR. The cardiovascular and kidney benefits persist independent of glycemic effects. 9
Do not mistake the initial reversible eGFR dip (hemodynamic effect) as a reason to discontinue therapy. This is an expected physiologic response that does not indicate kidney injury. 9
Monitor for euglycemic diabetic ketoacidosis, particularly during acute illness, surgery, or periods of reduced oral intake. Educate patients to seek medical attention for symptoms of ketoacidosis even with normal glucose levels. 1, 5, 10
Counsel patients about increased risk of genital mycotic infections, which can be managed with hygiene counseling and are more common than urinary tract infections. 8, 6, 10