SGLT2 Inhibitor Names
The currently available SGLT2 inhibitors are empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin. 1
FDA-Approved SGLT2 Inhibitors
The four SGLT2 inhibitors approved for clinical use in the United States are:
- Empagliflozin - Demonstrated cardiovascular mortality reduction in the EMPA-REG OUTCOME trial 1, 2
- Canagliflozin - Showed cardiovascular benefit in the CANVAS/CANVAS-R trials 1
- Dapagliflozin - Proven cardiovascular and renal benefits with high selectivity for SGLT2 over SGLT1 3, 4
- Ertugliflozin - Among the most selective SGLT2 inhibitors, though with less extensive cardiovascular outcomes data 3, 5
Additional SGLT2 Inhibitor
- Sotagliflozin - A dual SGLT1/SGLT2 inhibitor that differs from the four primary agents due to its combined mechanism 3, 6
Key Distinguishing Features
Selectivity profiles vary among agents: Dapagliflozin, empagliflozin, and ertugliflozin demonstrate the highest selectivity for SGLT2 compared to SGLT1, while canagliflozin has greater SGLT1 inhibition affecting intestinal glucose absorption 3
All four primary agents share the same core mechanism: They block sodium-glucose co-transporter 2 proteins in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion 5, 2, 7
Clinical Context
These medications provide benefits beyond glucose lowering: All SGLT2 inhibitors reduce HbA1c by 0.5-1.0%, promote weight loss of 1.5-3.5 kg, and lower systolic blood pressure by 3-5 mmHg 8, 5, 9
Cardiovascular and renal protection persists even when glycemic efficacy declines: The cardiorenal benefits continue down to eGFR levels of 20-30 mL/min/1.73 m², well below the threshold where glucose-lowering effects are minimal 3
Important Safety Considerations
Common cautions apply across the class: Increased risk of mycotic genital infections, euglycemic ketoacidosis in vulnerable patients, and volume depletion particularly in elderly patients or those on diuretics 1
Agent-specific warnings exist: Canagliflozin carries increased risk of bone fractures, osteoporosis concerns, and lower extremity amputations in patients with prior amputation history, severe peripheral vascular disease, or diabetic foot ulcers 1, 9