Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of prescription medications that have emerged as a significant advancement in managing certain health conditions. These drugs represent a relatively new approach to treatment, operating through a unique biological mechanism within the body. Their primary purpose extends beyond initial expectations, offering benefits for complex and interconnected health issues.
How SGLT2 Inhibitors Work
The kidneys play a central role in filtering blood and maintaining the body’s balance of substances, including glucose. As blood passes through the kidneys, filtering units allow glucose to pass into the tubules. Normally, almost all of the filtered glucose is reabsorbed back into the bloodstream for energy.
This reabsorption is largely handled by a specific protein known as sodium-glucose cotransporter 2 (SGLT2). SGLT2 is responsible for reabsorbing approximately 90% of the glucose that has been filtered. SGLT2 inhibitors work by blocking the function of this protein, preventing it from reabsorbing glucose.
When SGLT2 is blocked, less glucose is reabsorbed into the bloodstream. This leads to a greater amount of glucose remaining in the kidney tubules and subsequently being excreted from the body through urine. This process also results in the excretion of some sodium and water along with the glucose, contributing to a mild diuretic effect. The mechanism of action is independent of insulin.
Primary Medical Applications
SGLT2 inhibitors are prescribed for several important medical conditions. They were initially developed to help manage blood glucose levels in adults with type 2 diabetes. By increasing glucose excretion in the urine, these medications effectively lower blood sugar and improve glycated hemoglobin (HbA1c) levels.
Beyond diabetes, SGLT2 inhibitors have demonstrated benefits for patients with heart failure. They are used in individuals with heart failure, whether they have reduced or preserved ejection fraction, improving outcomes regardless of their diabetes status. This class of drugs has become a standard of care for cardiovascular protection in people with type 2 diabetes and those with heart failure.
SGLT2 inhibitors also manage chronic kidney disease (CKD). They help slow the progression of kidney disease, even in patients without diabetes. This protective effect on the kidneys is observed across a broad spectrum of CKD patients.
Broad Health Benefits
SGLT2 inhibitors offer health benefits beyond glucose-lowering. A significant benefit involves cardiovascular protection, particularly for individuals with type 2 diabetes and existing cardiovascular disease or multiple risk factors. These medications reduce the risk of major adverse cardiovascular events, including heart attack, stroke, and cardiovascular death. This protective effect helps improve overall heart health outcomes.
The medications also provide kidney protection, reducing the risk of kidney disease progression, end-stage renal disease, and kidney-related death. This protective effect is seen in various patient groups, extending to those with and without diabetes. SGLT2 inhibitors achieve this by influencing factors like blood pressure and uric acid levels.
Patients taking SGLT2 inhibitors often experience modest weight loss. This occurs due to the increased excretion of glucose and calories in the urine. Additionally, these medications have a mild effect on lowering blood pressure, contributing to overall cardiovascular well-being.
Potential Side Effects and Important Considerations
While SGLT2 inhibitors offer benefits, patients should be aware of potential side effects and important considerations. Common side effects include an increased risk of urinary tract infections (UTIs) and yeast infections. This occurs due to the higher glucose levels present in the urine. Maintaining good hygiene and staying hydrated can help mitigate the risk of these infections.
More serious side effects can occur. Diabetic ketoacidosis (DKA), a rare but serious condition where ketones build up, can occur even with normal blood glucose. Symptoms of DKA include nausea, vomiting, abdominal pain, excessive thirst, and unusually deep or fast breathing. Another very rare but severe complication is Fournier’s gangrene, a rapidly progressing bacterial infection of the genital or perineal area, requiring immediate medical attention.
SGLT2 inhibitors can also lead to dehydration and orthostatic hypotension, a sudden drop in blood pressure upon standing. This risk is higher in older adults or those also taking diuretics. Healthcare providers monitor kidney function and blood pressure. SGLT2 inhibitors are not recommended for patients with severe kidney impairment, those on dialysis, or individuals with type 1 diabetes. Patients should stay well-hydrated and promptly report any concerning symptoms to their healthcare provider.