From the Guidelines
Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that works by blocking glucose reabsorption in the proximal tubules of the kidneys, leading to increased glucose excretion in the urine and subsequent lowering of blood glucose levels.
Mechanism of Action
The mechanism of action of empagliflozin involves the selective inhibition of SGLT2 proteins located in the early portion of the nephron, which are responsible for reabsorbing approximately 90% of filtered glucose from the urine back into the bloodstream 1. By inhibiting these transporters, empagliflozin prevents glucose reabsorption, causing excess glucose to be excreted in the urine (glucosuria). This effectively lowers blood glucose levels independent of insulin action, making it particularly valuable for type 2 diabetes management.
Key Effects
Some key effects of empagliflozin include:
- Increased urinary glucose excretion leading to caloric loss and mild diuresis, contributing to weight reduction and blood pressure lowering effects
- Cardioprotective benefits through reduced cardiac preload and afterload, decreased inflammation, and improved energy metabolism in the heart
- Renoprotective benefits through reduced intraglomerular pressure in the kidneys These multiple effects explain why empagliflozin is beneficial not only for glycemic control but also for cardiovascular and renal outcomes in patients with type 2 diabetes, as demonstrated in studies such as EMPA-REG OUTCOME 1 and EMPEROR-Reduced 1.
From the FDA Drug Label
Empagliflozin is an inhibitor of SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion
The mechanism of action of Empagliflozin is the inhibition of SGLT2, which leads to:
- Reduction of renal reabsorption of filtered glucose
- Lowering of the renal threshold for glucose
- Increase in urinary glucose excretion Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule, which may influence several physiological functions, including:
- Increasing tubuloglomerular feedback
- Reducing intraglomerular pressure
- Lowering both pre- and afterload of the heart
- Downregulating sympathetic activity 2
From the Research
Mechanism of Action of Empagliflozin
The mechanism of action of Empagliflozin, an SGLT2 inhibitor, is as follows:
- Empagliflozin works by inhibiting the sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules of the kidneys, which reduces glucose reabsorption and increases urinary glucose excretion 3, 4.
- This mechanism of action is not insulin-dependent or insulin-sensitive, making it suitable for use in patients with different stages of diabetes and nonfunctional or impaired pancreatic β cells 3.
- The inhibition of SGLT2 by empagliflozin reduces the renal threshold for glucose and increases the amount of glucose excreted in the urine, thereby lowering blood glucose levels 3, 5.
Effects on the Kidneys and Cardiovascular System
The effects of empagliflozin on the kidneys and cardiovascular system are:
- Empagliflozin reduces kidney weight and urinary albumin/creatinine ratio in diabetic mice, indicating a potential renoprotective effect 5.
- The drug also prevents glomerular hyperfiltration and reduces blood pressure in diabetic mice, suggesting a beneficial effect on cardiovascular health 5, 6.
- Clinical trials have shown that empagliflozin reduces the risk of cardiovascular mortality, major cardiovascular events, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk 6, 7.
Potential Molecular Mechanisms
Potential molecular mechanisms underlying the beneficial effects of empagliflozin on diabetic cardiomyopathy include: