Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of prescription medications that help manage several health conditions by influencing kidney function. These medications are also referred to as gliflozins. Their primary action involves altering how the kidneys process glucose, leading to various beneficial effects in the body. SGLT2 inhibitors are taken orally, typically once a day.
How They Work
SGLT2 inhibitors target sodium-glucose cotransporter 2 (SGLT2) proteins in the kidneys. These proteins are located in the proximal convoluted tubule, an early segment of the kidney’s filtering units known as nephrons. The SGLT2 proteins are responsible for reabsorbing about 90% of the glucose filtered from the blood back into the bloodstream.
By blocking the action of these SGLT2 proteins, the inhibitors prevent the kidneys from reabsorbing as much glucose. This blockage leads to an increased amount of glucose being excreted from the body through urine, a process known as glucosuria. This mechanism operates independently of insulin, meaning it can lower blood sugar without directly affecting insulin secretion or sensitivity.
The increased excretion of glucose in the urine also results in the excretion of sodium and water, a process called natriuresis and osmotic diuresis. This mild diuretic effect can contribute to a reduction in plasma volume and blood pressure. These combined actions of reducing glucose reabsorption and promoting sodium and water excretion contribute to the therapeutic benefits of SGLT2 inhibitors.
Medical Conditions They Address
SGLT2 inhibitors were initially developed to manage blood glucose levels in people with type 2 diabetes, but clinical trials have revealed broader benefits for heart and kidney health.
Type 2 Diabetes
For individuals with type 2 diabetes, SGLT2 inhibitors improve glycemic control by lowering blood sugar levels. This action can lead to a reduction in hemoglobin A1c (HbA1c) levels, a measure of average blood sugar over several months, typically by 0.5% to 1%. These medications can be used alone or in combination with other diabetes treatments, such as metformin.
Heart Failure
SGLT2 inhibitors have demonstrated significant benefits for patients with heart failure, regardless of their diabetes status. They reduce hospitalizations for heart failure and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF). Emerging evidence also supports their effectiveness in patients with heart failure with preserved ejection fraction (HFpEF, a condition where the heart muscle contracts normally but the ventricles do not relax properly).
The mechanisms behind these heart benefits are complex and may include reducing fluid overload, improving cardiac metabolism, and decreasing inflammation and fibrosis within the heart. This class of medication is now an important treatment for heart failure across the spectrum of ejection fractions.
Chronic Kidney Disease (CKD)
SGLT2 inhibitors offer protective effects for the kidneys, slowing the progression of kidney disease in patients with and without diabetes. They reduce the risk of kidney failure and decrease levels of albuminuria, a marker of kidney damage where protein leaks into the urine. This protective action is thought to be partly due to lowering pressure in the tiny filtering units of the kidneys, called glomeruli.
Clinical trials have shown that SGLT2 inhibitors can slow the decline in estimated glomerular filtration rate (eGFR), a measure of kidney function. They also reduce the risk of severe kidney outcomes, such as a sustained 50% decrease in eGFR or progression to end-stage kidney disease. These benefits extend to patients with advanced CKD, even when the glucose-lowering effect may be diminished due to lower kidney function.
Important Considerations for Patients
Patients considering or currently taking SGLT2 inhibitors should be aware of potential side effects and monitoring requirements. Common side effects often include increased urination, which can lead to thirst or dehydration. Due to the increased glucose in the urine, individuals may experience a higher risk of genital yeast infections and urinary tract infections. Maintaining good personal hygiene and hydration can help manage these issues.
While generally safe, rare but serious side effects can occur. These include diabetic ketoacidosis (DKA), a condition where the body produces high levels of acids called ketones, which can happen even with normal blood sugar levels. Another rare but serious infection is Fournier’s gangrene, a rapidly progressing infection of the genital area. Patients should seek immediate medical attention if they experience symptoms such as severe pain, tenderness, redness, or swelling in the genital area, especially if accompanied by fever or general unwellness. Symptoms of DKA include nausea, vomiting, abdominal pain, extreme tiredness, or rapid breathing.
Regular medical check-ups and monitoring are important when taking SGLT2 inhibitors. This includes periodic blood tests to assess kidney function, as a slight, temporary decrease in estimated glomerular filtration rate (eGFR) can occur initially as the body adjusts. While this initial dip is acceptable, kidney function should be monitored, especially in patients with pre-existing kidney conditions.
SGLT2 inhibitors are not recommended for individuals with severe kidney impairment, end-stage kidney disease, or those on dialysis. They are also not approved for type 1 diabetes. Your healthcare provider may advise temporarily stopping the medication before certain surgical procedures or during acute illnesses to minimize risks like volume depletion or ketoacidosis.