What is a good Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitor?

From the Guidelines

Empagliflozin (Jardiance) is the most effective SGLT2 inhibitor for patients with type 2 diabetes, especially those with cardiovascular disease or chronic kidney disease, as it has been shown to reduce the relative risk for hospitalization from heart failure by 35% 1.

Key Considerations

• The typical starting dose of empagliflozin is 10 mg once daily, which can be increased to 25 mg daily if needed for better glycemic control.
• Other excellent options include dapagliflozin (Farxiga) at 5-10 mg daily and canagliflozin (Invokana) at 100-300 mg daily.
• These medications work by preventing glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine, which lowers blood sugar levels.
• Beyond glucose control, SGLT2 inhibitors offer significant cardiovascular and renal protection, reducing heart failure hospitalizations and slowing kidney disease progression, as seen in the EMPA-REG OUTCOME trial, CANVAS Program, and DECLARE-TIMI 58 study 1.

Important Safety Considerations

• Common side effects include genital yeast infections and increased urination.
• These medications should be used cautiously in patients with history of diabetic ketoacidosis, severe kidney disease, or recurrent urinary tract infections.
• They should be temporarily discontinued during acute illness or before surgical procedures to prevent dehydration or ketoacidosis, following a sick day protocol and periprocedural/perioperative care guidelines 1.

Patient Selection and Monitoring

• Eligible patients should have an eGFR ≥20 ml/min per 1.73 m2 and high priority features such as ACR ≥200 mg/g [≥20 mg/mmol] 1.
• Patient selection should consider potential contraindications, such as genital infection risk, diabetic ketoacidosis, foot ulcers, and immunosuppression.
• Education and follow-up are crucial to assess adverse effects, review knowledge, and anticipate an acute drop in eGFR, which is generally not a reason to stop the SGLT2 inhibitor 1.

From the FDA Drug Label

The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S). Empagliflozin is a white to yellowish, non-hygroscopic powder. 12. 1 Mechanism of Action Sodium-glucose co-transporter 2 (SGLT2) is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Empagliflozin is an inhibitor of SGLT2 By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

Empagliflozin and dapagliflozin are both SGLT2 inhibitors.

• Empagliflozin is an orally-active inhibitor of the sodium-glucose co-transporter 2 (SGLT2)
• Dapagliflozin is an inhibitor of SGLT2, which reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion Both can be considered good SGLT2 inhibitors, but the choice between them depends on individual patient factors and clinical considerations 2 3.

From the Research

Characteristics of a Good SGLT2 Inhibitor

• A good SGLT2 inhibitor should be effective in lowering glucose levels in patients with type 2 diabetes, as seen with empagliflozin 4.
• It should have a favorable effect on nonglycemic outcomes, such as modest reductions in body weight and blood pressure, as observed with empagliflozin 4 and other SGLT2 inhibitors 5, 6.
• A good SGLT2 inhibitor should also have cardioprotective and renoprotective properties, as demonstrated by empagliflozin in the EMPA-REG OUTCOME trial 4, 7.

Examples of Good SGLT2 Inhibitors

• Empagliflozin (Jardiance®) is a potent, highly selective SGLT2 inhibitor that has been shown to be effective and generally well-tolerated in patients with type 2 diabetes 4.
• Other SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and ertugliflozin, have also been found to have beneficial effects on glycemic control and nonglycemic outcomes 5, 6, 8.

Considerations for Choosing an SGLT2 Inhibitor

• The choice of SGLT2 inhibitor may depend on the individual patient's characteristics, such as the presence of cardiovascular disease or chronic kidney disease 7, 5.
• Empagliflozin may be preferred over canagliflozin in patients with osteoporosis or prior amputation due to the increased risk of bone fractures and amputations associated with canagliflozin 5.
• The potential risks and benefits of SGLT2 inhibitors, including the risk of genitourinary infections, dehydration, and diabetic ketoacidosis, should be carefully considered when selecting a treatment option 6, 8.