Vildagliptin

Usage

• Vildagliptin is prescribed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. It can be used as monotherapy, or in combination with other antidiabetic agents like metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) when diet and exercise plus the previous therapy do not provide adequate glycemic control.
• Pharmacological Classification: Dipeptidyl peptidase-4 (DPP-4) inhibitor, Antidiabetic agent.
• Mechanism of Action: Vildagliptin inhibits the enzyme DPP-4, which is responsible for the inactivation of incretin hormones like GLP-1 and GIP. These hormones play a crucial role in glucose homeostasis by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. By preventing their breakdown, vildagliptin enhances incretin action, leading to improved glycemic control.

Alternate Names

• International Nonproprietary Name (INN): Vildagliptin
• Brand Names: Galvus, Galvusmet (in combination with Metformin)

How It Works

• Pharmacodynamics: Vildagliptin primarily exerts its glucose-lowering effect by increasing the levels of active incretin hormones (GLP-1 and GIP). This leads to increased insulin secretion from pancreatic beta-cells and decreased glucagon secretion from alpha-cells, primarily when blood glucose levels are elevated. The glucose-dependent nature of this mechanism reduces the risk of hypoglycemia.
• Pharmacokinetics:
  • Absorption: Vildagliptin is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1.75 hours. Food intake does not significantly affect its absorption.
  • Metabolism: Vildagliptin is primarily metabolized by hydrolysis to its major metabolite, LAY151, which is pharmacologically inactive. CYP450 enzymes play a minor role in its metabolism.
  • Elimination: Approximately 85% of the dose is excreted in the urine (69% as metabolites and 16% as unchanged drug), with the remaining 15% eliminated in the feces. The elimination half-life is about 3 hours.
• Mode of Action: Vildagliptin selectively and reversibly inhibits DPP-4.
• Receptor Binding/Enzyme Inhibition: It binds to and inhibits DPP-4, thereby preventing the degradation of GLP-1 and GIP.
• Elimination Pathways: Primarily renal excretion (both as metabolites and unchanged drug), with minor hepatic elimination through the feces.

Dosage

Standard Dosage

Adults:

• The recommended dose is 50 mg once or twice daily. The maximum daily dose is 100 mg.

• Monotherapy and combination with metformin, a TZD, or insulin (with or without metformin): 50 mg or 100 mg daily (divided into two doses: 50 mg in the morning and 50 mg in the evening.)

• Dual combination with a sulfonylurea: 50 mg once daily in the morning (higher doses not shown to be more effective.)

Children:

• Use in patients under 18 years of age is not recommended due to lack of data.

Special Cases:

• Elderly Patients: No dose adjustment is necessary unless there is renal impairment.
• Patients with Renal Impairment:
  • Mild Renal Impairment: No dosage adjustment is required.
  • Moderate or Severe Renal Impairment or ESRD: 50 mg once daily in the morning.
• Patients with Hepatic Dysfunction: Vildagliptin is not recommended.
• Patients with Comorbid Conditions: Dosage adjustment may be necessary based on the specific comorbidity.

Clinical Use Cases

Vildagliptin is not indicated for use in the following clinical settings:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status epilepticus, cardiac arrest)

Dosage Adjustments

Dose adjustments may be required based on renal function, hepatic function, and concomitant medications (e.g., sulfonylureas).

Side Effects

Common Side Effects

• Headache
• Dizziness
• Nasopharyngitis
• Peripheral edema
• Tremor

Rare but Serious Side Effects

• Angioedema
• Pancreatitis
• Hepatic dysfunction (including hepatitis)

Long-Term Effects

Long-term effects are still being studied, but no specific chronic complications have been consistently associated with prolonged vildagliptin use.

Adverse Drug Reactions (ADR)

Clinically significant ADRs include angioedema, pancreatitis, and hepatic dysfunction, all requiring immediate medical attention.

Contraindications

• Hypersensitivity to vildagliptin.
• Type 1 diabetes.
• Diabetic ketoacidosis.
• Moderate or severe renal impairment or ESRD.
• Hepatic impairment.

Drug Interactions

• Vildagliptin has a low potential for drug interactions due to its metabolism pathway primarily involving hydrolysis rather than CYP450 enzymes.
• No clinically significant interactions have been observed with metformin, sulfonylureas, thiazolidinediones, digoxin, warfarin, simvastatin, ramipril, valsartan or amlodipine. Concomitant administration with ACE inhibitors may increase the risk of angioedema. Alcohol can also potentially alter glycemic levels, therefore, it is advisable to avoid consuming it with vildagliptin
• Thiazides, corticosteroids, thyroid products, and sympathomimetics may reduce the hypoglycemic effects of vildagliptin.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: There is insufficient data on the use of vildagliptin during pregnancy. It is not recommended for use in pregnant women.
• Breastfeeding: It is unknown if vildagliptin is excreted in human milk. It is not recommended for use in breastfeeding women.

Drug Profile Summary

• Mechanism of Action: DPP-4 inhibitor, enhancing incretin action.
• Side Effects: Headache, dizziness, nasopharyngitis, peripheral edema, tremor; rarely, angioedema, pancreatitis, hepatic dysfunction.
• Contraindications: Hypersensitivity, type 1 diabetes, diabetic ketoacidosis, moderate/severe renal/hepatic impairment.
• Drug Interactions: Low potential; possible increased angioedema risk with ACE inhibitors.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: 50 mg once or twice daily (max 100 mg/day); adjustments needed for certain conditions.
• Monitoring Parameters: HbA1c, fasting plasma glucose, renal and hepatic function.

Popular Combinations

• Metformin: Often combined with vildagliptin for synergistic glucose-lowering effects.

Precautions

• General Precautions: Assess renal and hepatic function before starting vildagliptin.
• Specific Populations: Avoid use during pregnancy and breastfeeding. Exercise caution in patients with a history of pancreatitis or heart failure. Not recommended for children under 18.
• Lifestyle Considerations: Advise patients to follow a healthy diet and exercise regularly. Alcohol should be avoided as it may increase the risk of lactic acidosis and interact with vildagliptin resulting in alteration of blood sugar levels.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Vildagliptin?

A: The recommended dose is 50 mg once or twice daily, with a maximum of 100 mg per day. Adjustments are necessary for patients with renal impairment and when used in combination with a sulfonylurea.

Q2: How does Vildagliptin differ from other antidiabetic medications?

A: Vildagliptin, a DPP-4 inhibitor, works by increasing incretin levels, offering a lower risk of hypoglycemia compared to sulfonylureas. Unlike thiazolidinediones, it does not cause weight gain or edema.

Q3: What are the most common side effects of Vildagliptin?

A: Headache, dizziness, nasopharyngitis, and peripheral edema are common.

Q4: Is Vildagliptin safe for patients with kidney disease?

A: Dosage adjustments are needed for moderate to severe renal impairment. It is not recommended in ESRD patients requiring hemodialysis.

Q5: Can Vildagliptin be used during pregnancy or breastfeeding?

A: No, it is not recommended for use during pregnancy or breastfeeding.

Q6: What should I do if my patient misses a dose of Vildagliptin?

A: The missed dose should be taken as soon as the patient remembers. However, a double dose should not be taken on the same day.

Q7: How does Vildagliptin interact with alcohol?

A: Excessive alcohol intake should be avoided as it may potentiate the risk of lactic acidosis, and alter glycemic levels which can either increase or decrease blood sugar levels.

Q8: What are the monitoring parameters for patients on Vildagliptin?

A: Monitor HbA1c, fasting blood glucose, renal function, and hepatic function tests.

Q9: Can Vildagliptin be used with other antidiabetic agents?

A: Yes, Vildagliptin can be used with metformin, sulfonylureas, thiazolidinediones, and insulin.

Q10: Can Vildagliptin cause hypoglycemia?

A: Vildagliptin monotherapy carries a low risk of hypoglycemia. However, the risk increases when combined with other antidiabetic agents, especially sulfonylureas. A lower dose of the sulfonylurea may be considered.