Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors are a class of medications developed to address various health conditions. SGLT2 stands for sodium-glucose cotransporter 2, a protein in the kidneys. These drugs were approved by the FDA for diabetes treatment in 2013.
How They Work
SGLT2 inhibitors primarily act on the kidneys, which regulate blood glucose levels. Normally, as blood flows through the kidneys, glucose is filtered out and largely reabsorbed back into the bloodstream by proteins like SGLT2. The SGLT2 protein, located in the early part of the kidney tubules, reabsorbs approximately 90% of the filtered glucose.
SGLT2 inhibitors block this protein’s activity. This prevents the kidneys from reabsorbing most glucose back into the blood. This action leads to increased excretion of glucose, sodium, and water through the urine. Consequently, blood sugar levels are lowered, and this mechanism operates independently of insulin.
Therapeutic Uses and Beyond
SGLT2 inhibitors were initially used for managing type 2 diabetes. They improve glycemic control by helping the body remove excess sugar through urine, reducing hemoglobin A1c levels by about 0.5% to 1%. This glucose-lowering effect does not cause low blood sugar (hypoglycemia) when these medications are used alone.
Beyond blood sugar management, SGLT2 inhibitors have demonstrated benefits for cardiovascular and kidney health. Clinical trials show their ability to reduce the risk of heart failure hospitalization and cardiovascular death. These benefits extend to patients with heart failure regardless of type 2 diabetes or ejection fraction.
These medications also improve kidney function by slowing the progression of chronic kidney disease (CKD). They reduce pressure within the kidney’s filtering units, preserving kidney function over time. This renoprotective effect has been observed in individuals with CKD, even without diabetes.
Important Information for Patients
Patients considering SGLT2 inhibitors should be aware of potential side effects and precautions. Common side effects include urinary tract infections and genital yeast infections, occurring due to increased glucose in the urine. Dehydration symptoms, such as dizziness or lightheadedness, can also occur from increased fluid excretion.
Less common but serious side effects include diabetic ketoacidosis (DKA), a condition where the body produces high levels of blood acids called ketones. While rare, DKA can occur even with normal or slightly elevated blood sugar levels, particularly in type 2 diabetes patients. Another rare but severe complication is Fournier’s gangrene, a rapidly progressing bacterial infection of the genital or perineal area.
SGLT2 inhibitors are not recommended for individuals with type 1 diabetes due to higher DKA risk. They are also contraindicated in people with severe kidney disease or those on dialysis. Patients should discuss their medical history with a healthcare provider, including any history of frequent infections or severe liver disease. Adhere to prescribed dosages and temporarily stop the medication during acute illnesses or before surgery, as advised by a doctor.