Examples of Sodium Glucose Transporter 2 (SGLT2) Inhibitors
Dapagliflozin, empagliflozin, and canagliflozin are the most common examples of SGLT2 inhibitors used in the treatment of type 2 diabetes mellitus. 1, 2
Mechanism of Action
- SGLT2 inhibitors work by blocking the sodium-glucose co-transporter 2 proteins in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion 3
- These medications lower the renal threshold for glucose (RTG), promoting glucosuria when blood glucose levels exceed approximately 180 mg/dL 2, 3
- Unlike other antidiabetic medications, SGLT2 inhibitors function independently of insulin secretion or action, making them effective regardless of diabetes duration 2
- Canagliflozin specifically inhibits SGLT2 expressed in the S1 and S2 segments of the proximal convoluted tubule in the kidneys 3
Available SGLT2 Inhibitors
- Dapagliflozin - a selective SGLT2 inhibitor available in 5mg and 10mg oral tablets 4
- Empagliflozin - highly selective for SGLT2 receptors 1, 2
- Canagliflozin - first-in-class SGLT2 inhibitor approved in the United States 5
- Ertugliflozin - another selective SGLT2 inhibitor 1, 2
- Sotagliflozin - considered a "dual SGLT1/SGLT2 inhibitor" with greater affinity for SGLT1 receptors 1
Clinical Benefits
- Reduction in HbA1c levels by approximately 0.5% to 1.0% 1, 6
- Weight loss of 1.5 to 3.5 kg 1, 7
- Lowering of systolic blood pressure by 3 to 5 mmHg 1, 6
- Reduced risk of major cardiovascular adverse events 1
- Decreased hospitalization rates for heart failure 1
- Renoprotective effects with reduced progression of diabetic kidney disease 1
- Low risk of hypoglycemia when used as monotherapy 1, 8
Safety Profile and Adverse Effects
- Most common adverse effects include genital mycotic infections, particularly in women (10% vs 3% with placebo) 8
- Urinary tract infections occur in approximately 9% of women treated with canagliflozin compared to 7% with placebo 8
- Increased urination due to osmotic diuresis 8, 7
- Rare adverse events include diabetic ketoacidosis, acute kidney injury, and bone fractures 1
- Canagliflozin specifically has been associated with potential increased risk of lower extremity amputations 1, 6
- Dose adjustments are required in patients with moderate renal impairment, and these medications should be discontinued in severe renal impairment 1
Pharmacokinetics
- Canagliflozin reaches peak plasma concentrations within 1-2 hours after oral administration 3, 9
- The oral bioavailability of canagliflozin is approximately 65% 3, 9
- Terminal half-life ranges from 10.6 hours (100mg dose) to 13.1 hours (300mg dose) for canagliflozin 3, 9
- Steady-state is typically reached after 4-5 days of once-daily dosing 3, 9
Emerging Research
- Recent studies suggest SGLT2 inhibitors may have neuroprotective properties due to the presence of SGLT2 in the Central Nervous System 1
- Potential benefits in cognitive function in patients with type 2 diabetes mellitus are being investigated 1
- SGLT2 inhibitors are increasingly recognized for their cardiorenal protective effects even in individuals without diabetes 6
SGLT2 inhibitors represent an important class of medications for type 2 diabetes management with benefits extending beyond glycemic control to include cardiovascular and renal protection.