Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a class of medications with therapeutic effects beyond their initial intended use. While originally developed to manage blood sugar in individuals with type 2 diabetes, these inhibitors have demonstrated a broader impact on health. Their emerging role in supporting heart health has reshaped treatment approaches for various cardiovascular conditions.
Understanding SGLT2 Inhibitors
SGLT2 inhibitors are oral prescription medications. Their primary mechanism of action involves the kidneys, targeting the SGLT2 protein in the renal tubules. This protein is responsible for reabsorbing most filtered glucose back into the bloodstream.
By blocking the SGLT2 protein, these inhibitors prevent the kidneys from reabsorbing a significant portion of filtered glucose, leading to increased glucose excretion in the urine. This process, known as glucosuria, helps lower blood glucose levels. Canagliflozin was the first SGLT2 inhibitor approved by the FDA in March 2013 for the management of type 2 diabetes, followed by dapagliflozin and empagliflozin in 2014.
How SGLT2 Inhibitors Protect the Heart
SGLT2 inhibitors offer various benefits for heart health beyond their glucose-lowering effects. One mechanism involves improved kidney function, as these inhibitors reduce pressure within the kidney’s filtering units, known as glomeruli. This helps alleviate hyperfiltration, a condition where kidneys work too hard, potentially leading to damage.
The medications also reduce fluid overload by increasing the excretion of sodium and water through urine, a process called natriuresis and diuresis. This fluid reduction can lead to a sustained decrease in both systolic and diastolic blood pressure. This mild diuretic effect lessens the heart’s workload.
Another mechanism is improved myocardial energy efficiency, where the heart muscle may utilize alternative fuel sources like ketone bodies more effectively. SGLT2 inhibitors also exhibit anti-inflammatory and anti-oxidant properties, which can help reduce inflammation and oxidative stress that contribute to cardiovascular disease progression. These multifaceted actions collectively contribute to their cardioprotective effects.
Who Benefits from SGLT2 Inhibitors
SGLT2 inhibitors are prescribed for several patient populations due to their cardioprotective and renoprotective effects, moving beyond their initial use solely for type 2 diabetes. Individuals with heart failure, regardless of their ejection fraction, can benefit from these medications. This includes patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
The benefits extend to patients with chronic kidney disease (CKD), whether or not they have diabetes. SGLT2 inhibitors have been shown to slow the progression of CKD and reduce the risk of kidney failure. For individuals with type 2 diabetes who also have established cardiovascular disease or multiple cardiovascular risk factors, SGLT2 inhibitors are recommended to lower the risk of major adverse cardiovascular events, including heart attack and stroke.
Important Considerations for SGLT2 Inhibitors
While SGLT2 inhibitors offer significant benefits, potential side effects and considerations exist. Common side effects include increased urination frequency, mild dehydration, and a higher likelihood of genitourinary infections, such as yeast infections or urinary tract infections, due to increased glucose in the urine. Patients may also experience a slight, temporary decrease in kidney function at the start of treatment as the body adjusts.
SGLT2 inhibitors are prescription-only medications and require ongoing medical supervision. They are generally not recommended for individuals with severe kidney impairment (eGFR below 30 mL/min/1.73m²) or those on dialysis, as their effectiveness is limited. Patients should discuss their full medical history with a healthcare professional to determine if this class of medication is appropriate for their specific health needs.