MECHANISM OF ACTION:

SGLT2 inhibitors are a class of medications used to treat type 2 diabetes by lowering blood glucose levels through a renal mechanism. Here’s a concise overview of their mechanism of action:

1. Glucose Filtration in the Kidneys:

   • Blood is filtered in the kidneys, and glucose enters the renal tubules.

2. SGLT2 Function:

   • In the proximal tubule of the nephron, the SGLT2 (sodium-glucose cotransporter-2) protein reabsorbs glucose from the tubular fluid back into the bloodstream.

3. Inhibition by SGLT2 Inhibitors:

   • SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin) bind to and inhibit the SGLT2 proteins, blocking glucose reabsorption.

4. Increased Glucose Excretion:

   • With SGLT2 inhibited, glucose remains in the tubular fluid and is excreted in the urine, lowering blood glucose levels.

5. Systemic Effects:

   • Blood Glucose Control: Lowers blood sugar levels.

   • Weight Loss: Promotes weight loss due to caloric loss through glucose excretion.

   • Blood Pressure Reduction: May lower blood pressure due to diuretic effects.

   • Cardiovascular and Renal Benefits: Reduces risks of cardiovascular events and slows the progression of kidney disease.

By preventing glucose reabsorption in the kidneys, SGLT2 inhibitors effectively lower blood sugar levels and provide additional health benefits, making them a valuable treatment option for type 2 diabetes.

 SIDE Effects :

• Genital and Urinary Infections: Increased glucose in urine can lead to a higher risk of urinary tract infections and yeast infections.

• Dehydration: Can lead to an increased risk of dehydration due to the diuretic effect.

• Ketoacidosis: Rare but serious condition where blood becomes too acidic.

• Bone Fractures: Some studies suggest a potential increased risk of bone fractures.

uses :

SGLT2 inhibitors are primarily used for the management of type 2 diabetes. Their benefits extend beyond blood glucose control, offering advantages in weight management, cardiovascular health, and kidney function. Here are the key uses and benefits:

1. Management of Type 2 Diabetes:

• Lowering Blood Glucose Levels: SGLT2 inhibitors reduce blood sugar levels by promoting the excretion of glucose through the urine.

2. Cardiovascular Benefits:

• Reduction of Cardiovascular Events: Some SGLT2 inhibitors have been shown to reduce the risk of major cardiovascular events, including heart attack and stroke, in patients with type 2 diabetes who have established cardiovascular disease.

• Heart Failure: They can also reduce the risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors.

3. Renal (Kidney) Benefits:

• Protecting Kidney Function: SGLT2 inhibitors can slow the progression of kidney disease in patients with type 2 diabetes, reducing the risk of kidney failure.

4. Weight Loss:

• Weight Reduction: By promoting the excretion of excess glucose, SGLT2 inhibitors help in weight loss, which can be beneficial for many patients with type 2 diabetes. 

• 5. Blood Pressure Reduction:

• Lowering Blood Pressure: These medications can help reduce systolic blood pressure, providing an additional benefit for patients with hypertension.

PHARMACOKINETICS 

1. Absorption:

• Oral Bioavailability: SGLT2 inhibitors are orally administered and generally have good bioavailability.

• Time to Peak Concentration: They typically reach peak plasma concentrations (Tmax) within 1 to 2 hours after oral administration.

2. Distribution:

• Volume of Distribution (Vd): These drugs have a moderate volume of distribution, indicating they are well-distributed in body tissues.

• Protein Binding: SGLT2 inhibitors are highly bound to plasma proteins (generally > 90%), primarily albumin.

3. Metabolism:

• Primary Metabolism Pathways: These drugs are metabolized primarily by the liver through glucuronidation and, to a lesser extent, by the cytochrome P450 (CYP) enzyme system.

• Metabolites: The primary metabolites are generally inactive and are excreted in the urine and feces.

4. Excretion:

• Renal and Fecal Excretion: SGLT2 inhibitors and their metabolites are excreted through both urine and feces. The parent drug and its metabolites can be found in both.

• Half-Life: The elimination half-life varies among different SGLT2 inhibitors but typically ranges from 10 to 18 hours, allowing for once-daily dosing.