Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral prescription medications. Initially developed to manage blood sugar levels in adults with type 2 diabetes, their role in medicine has expanded. These medications offer benefits for other conditions, leading to their use in patients without diabetes to treat certain types of heart failure and chronic kidney disease.
How SGLT2 Inhibitors Work in the Body
The primary function of the kidneys is to filter waste from the blood while reabsorbing necessary substances like glucose. This reabsorption process is largely facilitated by a protein known as sodium-glucose cotransporter 2, or SGLT2, located in the kidneys. This protein is responsible for reclaiming about 90% of the glucose that is filtered by the kidneys, returning it to the bloodstream.
SGLT2 inhibitor medications function by selectively blocking the action of this SGLT2 protein. By doing so, they prevent the kidneys from reabsorbing a significant amount of glucose from the filtered fluid. This action lowers the renal threshold for glucose, which is the point at which glucose begins to be excreted in the urine.
Consequently, the excess glucose that would have been returned to the circulation is instead passed out of the body through urination. This process, known as glucosuria, directly lowers the concentration of glucose in the blood. This mechanism is independent of the body’s insulin levels or its sensitivity to insulin, distinguishing it from many other classes of diabetes medications.
Conditions Treated by SGLT2 Inhibitors
The most well-known application for SGLT2 inhibitors is managing type 2 diabetes. These medications lower blood sugar levels, which contributes to a reduction in hemoglobin A1c, a key long-term marker of glucose control. The American Diabetes Association includes SGLT2 inhibitors as a potential first-line therapy option, often with metformin, for specific patients with type 2 diabetes.
Beyond diabetes, SGLT2 inhibitors have emerged as a treatment for heart failure, including in patients who do not have diabetes. Clinical studies have demonstrated that these medications can reduce the risk of hospitalization for heart failure and death from cardiovascular causes. For individuals with heart failure, SGLT2 inhibitors can improve symptoms and reduce the chances of the heart’s condition worsening.
These medications also play a protective role in patients with chronic kidney disease (CKD). They have been shown to slow the progression of kidney disease and preserve kidney function over time. By reducing pressure within the kidneys, SGLT2 inhibitors help lower the risk of a significant decline in the glomerular filtration rate (eGFR), a measure of kidney function. This makes them a valuable therapeutic option for patients with CKD.
Common SGLT2 Inhibitor Medications
SGLT2 inhibitors are available as oral tablets and are prescribed under various names. The first medication in this class to receive FDA approval was canagliflozin in 2013.
Commonly prescribed SGLT2 inhibitors include:
- Canagliflozin (Invokana)
- Dapagliflozin (Farxiga)
- Empagliflozin (Jardiance)
- Ertugliflozin (Steglatro)
These can be prescribed as a standalone treatment or with other medications like metformin. The specific drug and dosage depend on an individual’s medical condition and overall health profile.
Potential Side Effects and Considerations
A primary consideration with SGLT2 inhibitors is their effect on the urinary system. Because these drugs cause sugar to be excreted in the urine, they create an environment where yeast and bacteria can more easily grow. This leads to an increased risk of genital yeast infections and a higher likelihood of developing urinary tract infections (UTIs).
The diuretic effect of these medications, which increases urination, can lead to intravascular volume depletion. This means patients are at a greater risk for dehydration and a drop in blood pressure, which may cause dizziness or fainting. It is often recommended that patients maintain adequate fluid intake, and a doctor might adjust the dosage of other diuretic medications to mitigate this risk.
A rare but serious side effect associated with this drug class is diabetic ketoacidosis (DKA), a condition where the body produces high levels of blood acids called ketones. SGLT2 inhibitors can sometimes cause euglycemic DKA, where ketoacidosis occurs without the typically high blood sugar levels, making it harder to diagnose. This is a medical emergency that requires immediate attention. The risk may be higher in individuals who are unwell, dehydrated, or about to undergo surgery.