What is the role of Sodium-Glucose Linked Transporter (SGLT)?

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Last updated: April 24, 2025View editorial policy

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From the Guidelines

SGLT2 inhibitors are recommended as a key treatment approach to reduce cardiovascular disease and heart failure outcomes in people with diabetes, particularly those with increased cardiovascular risk or established cardiovascular disease. The use of SGLT2 inhibitors has been shown to reduce the risk of major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes 1. Common SGLT2 inhibitors include empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin. These medications work by preventing glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine, which lowers blood sugar levels.

Key Benefits of SGLT2 Inhibitors

  • Reduce heart failure hospitalizations
  • Protect kidney function
  • Promote modest weight loss (typically 2-3kg)
  • Reduce the risk of major adverse cardiovascular events

Treatment Recommendations

  • People with type 2 diabetes and established ASCVD or established kidney disease should be treated with an SGLT2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit 1
  • In people with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or chronic kidney disease, an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events and/or heart failure hospitalization 1

Important Considerations

  • Patients should be monitored for diabetic ketoacidosis, especially during illness or fasting
  • These medications should be used cautiously in patients with reduced kidney function and are generally not recommended when eGFR falls below 30 ml/min/1.73m²
  • Common side effects include genital yeast infections, urinary tract infections, and volume depletion 1

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

  1. 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.
  • SGLT2 Inhibition: Empagliflozin is an inhibitor of the sodium-glucose co-transporter 2 (SGLT2), which is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation.
  • Mechanism of Action: By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, resulting in increased urinary glucose excretion 2, 2.

From the Research

SGLT2 Inhibitors

  • SGLT2 inhibitors, such as empagliflozin, are a class of drugs used to treat type 2 diabetes mellitus (T2DM) by reducing hyperglycemia through increased urinary glucose excretion 3, 4, 5, 6.
  • They have been shown to have favorable effects beyond glucose control, including reductions in body weight, blood pressure, and serum uric acid levels 3, 4, 5, 6.

Clinical Benefits

  • SGLT2 inhibitors have been demonstrated to have cardioprotective and renoprotective properties, reducing the risk of major adverse cardiovascular outcomes and improving renal outcomes in patients with T2DM and established cardiovascular disease (CVD) 3, 4, 5.
  • Empagliflozin, in particular, has been shown to reduce cardiovascular deaths and improve renal outcomes in patients with T2DM and established CVD 3, 4.

Safety and Tolerability

  • SGLT2 inhibitors are generally well tolerated, with a low risk of hypoglycemia and no significant weight gain 3, 4, 6.
  • However, they can increase the risk of genital mycotic infections, urinary tract infections, and events linked to volume depletion, such as dehydration and diabetic ketoacidosis 5, 6.

Treatment Recommendations

  • The use of SGLT2 inhibitors, such as empagliflozin, is recommended for patients with T2DM and established CVD or chronic kidney disease (CKD), as they have been shown to reduce the risk of major adverse cardiovascular outcomes and improve renal outcomes 4, 7.
  • For patients with T2DM and multiple cardiovascular risk factors, SGLT2 inhibitors may be considered as a treatment option to reduce the risk of CVD and CKD outcomes 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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