Sodium-glucose co-transporter 2 inhibitors, or SGLT2i, are a class of prescription oral medications designed to be used alongside diet and exercise. These medications are available as single-ingredient products or in combination with other drugs. Initially developed for diabetes management, their applications have expanded as research has revealed wider benefits.
How SGLT2 Inhibitors Work
The function of SGLT2 inhibitors centers on the kidneys. Under normal conditions, the kidneys filter blood, and specialized proteins called sodium-glucose co-transporters reabsorb glucose from this filtrate back into the bloodstream. The SGLT2 protein is a major transporter responsible for about 90% of this glucose reabsorption in the kidneys.
SGLT2 inhibitor medications work by selectively blocking these SGLT2 proteins. By obstructing this pathway, the drugs prevent the kidneys from reabsorbing a significant amount of glucose back into the body.
The result of this blockage is that excess glucose is flushed out of the body through the urine, a process known as glucosuria. This lowers the overall concentration of glucose in the blood. This process functions independently of the body’s insulin levels or sensitivity, which distinguishes it from many other diabetes treatments.
This removal of glucose via urine also causes a loss of calories, with daily losses estimated between 60 to 100 grams of glucose. The amount of glucose excreted can vary depending on the patient’s blood sugar levels; higher circulating glucose leads to greater excretion.
Approved Medical Uses
The Food and Drug Administration (FDA) has approved SGLT2 inhibitors for several medical conditions. Their primary approval was for improving blood sugar control in adults with type 2 diabetes when combined with diet and exercise.
Beyond diabetes, these drugs are approved for adults with heart failure to reduce the risk of hospitalization and death from cardiovascular causes. This benefit is linked to reducing fluid volume in the body, as the drugs also promote the excretion of sodium and water. This process eases the workload on the heart and reduces congestion.
Another approved use is for chronic kidney disease (CKD), as SGLT2 inhibitors slow the decline of kidney function and reduce the risk of kidney failure. The mechanism involves decreasing pressure within the glomeruli, the tiny filtering units inside the kidneys. This helps relax blood vessels within the kidney, lowering filtration pressure and preserving long-term kidney function.
Potential Side Effects
SGLT2 inhibitors are associated with a range of potential side effects. The most frequently reported issues are related to the presence of sugar in the urine. This sugar-rich environment can foster the growth of microorganisms, leading to an increased incidence of genital yeast infections and urinary tract infections (UTIs).
Other side effects stem from the medication’s diuretic effect, which can cause more frequent urination and increased thirst. In some individuals, like the elderly or those taking other diuretics, this fluid loss can lead to volume depletion, causing dizziness, lightheadedness, or low blood pressure (hypotension). Patients are advised to maintain adequate fluid intake to mitigate this risk.
Less common but more serious side effects have been identified. One is diabetic ketoacidosis (DKA), where the body produces high levels of blood acids called ketones. With SGLT2 inhibitors, this can occur at near-normal blood glucose levels, a state known as euglycemic DKA. Another rare but severe adverse event is Fournier’s gangrene, a serious infection of the genital area. Patients should discuss any side effects with their healthcare provider before stopping the medication.
Specific SGLT2 Inhibitor Medications
Several SGLT2 inhibitor medications are available, with generic names ending in “-flozin.” These are oral tablets taken once daily. While they share a common mechanism, their specific FDA-approved uses can differ slightly.
- Empagliflozin (Jardiance): This is approved for type 2 diabetes, heart failure, and to reduce the risk of cardiovascular death in adults with both type 2 diabetes and established heart disease.
- Dapagliflozin (Farxiga): This medication holds approvals for type 2 diabetes, heart failure, and chronic kidney disease.
- Canagliflozin (Invokana): This was the first SGLT2 inhibitor to be approved and is indicated for type 2 diabetes and to reduce cardiovascular risks and kidney disease complications in patients with type 2 diabetes.
- Ertugliflozin (Steglatro) and bexagliflozin (Brenzavvy): These are primarily approved to improve blood sugar control in adults with type 2 diabetes.
- Sotagliflozin (Inpefa): This medication blocks both SGLT2 and SGLT1, a transporter in the intestine, affecting glucose absorption from food. This dual-action inhibitor is approved to lower risks associated with heart failure.