SGLT2 inhibitors are a class of medications that target Sodium-Glucose Co-Transporter 2 (SGLT2), a protein found in the kidneys. These drugs influence how the kidneys handle glucose, offering a novel approach to managing various health conditions.
Understanding SGLT2 and Its Role
Sodium-Glucose Co-Transporter 2 (SGLT2) is a protein primarily located in the proximal tubules within the kidneys. Its main function is to reabsorb glucose from filtered blood back into the bloodstream. In healthy individuals, SGLT2 is responsible for reabsorbing approximately 90% of the glucose filtered by the kidneys. This process helps maintain glucose homeostasis, ensuring that minimal glucose is excreted in the urine. SGLT2 is highly efficient, preventing energy loss through glucosuria, or glucose in the urine. This reabsorption mechanism is a natural way the body conserves energy and nutrients.
How SGLT2 Inhibitors Work
SGLT2 inhibitors work by blocking the SGLT2 protein in the kidneys. By binding to SGLT2, these drugs prevent the reabsorption of glucose and sodium from the renal tubules back into the bloodstream. This leads to increased excretion of glucose and sodium through urine. As a result, SGLT2 inhibitors lower blood glucose levels without directly stimulating insulin release. This mechanism reduces the renal threshold for glucosuria, meaning glucose appears in the urine at lower blood sugar levels than usual. The process also increases natriuresis, the excretion of sodium in the urine, which contributes to a negative balance of salt and water, potentially lowering blood pressure.
Conditions Treated by SGLT2 Inhibitors
SGLT2 inhibitors were initially developed for type 2 diabetes, but their benefits extend to other medical conditions, impacting cardiovascular and renal health.
Type 2 Diabetes
For individuals with type 2 diabetes, SGLT2 inhibitors increase glucose excretion in the urine, which helps lower blood sugar levels and improves glycemic control. This can also lead to modest weight loss as the body expels excess calories. Common examples include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance).
Heart Failure
SGLT2 inhibitors play a role in treating heart failure. They reduce hospitalizations and cardiovascular death in patients with heart failure, regardless of diabetes status. This benefit is related to their ability to reduce fluid overload, lower blood pressure, and improve cardiac metabolism, easing the burden on the heart.
Chronic Kidney Disease
These medications also offer protection for patients with chronic kidney disease (CKD). SGLT2 inhibitors slow the progression of kidney disease and reduce the risk of kidney failure, even in patients without diabetes. They achieve this by lowering pressure within the kidney’s filtering units, preserving kidney function over time.
Potential Side Effects and Important Considerations
SGLT2 inhibitors offer significant health benefits, but it is important to be aware of their potential side effects. The increased glucose in the urine, a direct result of how these medications work, can lead to certain common adverse effects. These include an elevated risk of genital yeast infections and urinary tract infections, as the sugar creates a more favorable environment for bacterial and fungal growth. Dehydration and increased urination are also common due to the increased fluid excretion.
Less common but serious side effects warrant close attention. Diabetic ketoacidosis (DKA), a dangerous condition where the body produces high levels of ketones, has been reported in individuals taking SGLT2 inhibitors, even in those without diabetes or with well-controlled diabetes. Another rare but severe complication is Fournier’s gangrene, a rapidly progressing, life-threatening bacterial infection of the tissues around the genitals and perineum. While generally protective, SGLT2 inhibitors can also be associated with acute kidney injury in some cases.
Patients taking SGLT2 inhibitors should maintain proper hydration and practice good hygiene to mitigate the risk of infections. Any symptoms suggestive of serious side effects, such as severe pain, tenderness, redness, or swelling in the genital area accompanied by fever or general unwellness, require immediate medical attention. These medications are available by prescription only and require ongoing medical supervision to ensure their safe and effective use.