VILDARIL 50

Indications

• Type 2 diabetes mellitus as monotherapy if metformin is inappropriate
• Type 2 diabetes mellitus in combination with other antidiabetic drugs including insulin if glycemic control is not adequate with metformin alone

Dosage

Adults: 50 mg twice daily, or 100 mg once daily if used as monotherapy. In cases of renal impairment, reduce dose to 50 mg once daily.

Mechanism of action

Vildagliptin selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), which inactivates incretin hormones GLP-1 and GIP. By prolonging the half-life of these hormones, vildagliptin enhances insulin secretion in a glucose-dependent manner and reduces glucagon secretion. This leads to improved glucose homeostasis, reduction in fasting and postprandial glucose levels, and improved glycemic control in patients with type 2 diabetes mellitus.

Pharmacodynamics

Vildagliptin promotes glycemic control by increasing beta-cell sensitivity to glucose, enhancing glucose-dependent insulin secretion, and improving the insulin to glucagon ratio. It also decreases hepatic glucose production while having no effect on gastric emptying. Clinical studies have shown it effectively lowers glycated hemoglobin (HbA1c) and fasting plasma glucose levels in individuals with type 2 diabetes.

Pharmacokinetics

Vildagliptin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a half-life of approximately 2-3 hours. The drug is primarily excreted via the kidneys, with dose adjustments required for patients with renal impairment. It does not require adjustment for hepatic impairment. The pharmacokinetics may vary based on age and renal function.

Contra-indications

• History of pancreatitis
• Severe heart failure

Adverse effects

• Headache
• Dizziness
• Constipation
• Skin reactions
• Angioedema
• Back pain
• Cutaeous vasculitis
• Joint disorders
• Myalgia
• Acute pancreatitis
• Acute renal impairment
• Stevens-Johnson syndrome
• Vomiting

Interactions

• Dose of concomitant sulfonylurea or insulin may need to be reduced

Precautions

• Monitor renal function before treatment and periodically thereafter

Pregnancy

Avoid-toxicity in animal studies.

Breast-feeding

Avoid-present in milk in animal studies.

Storage

Store in a cool, dry place away from light.

Formulations

• Tablets: 50 mg
• Tablets: 100 mg

Mechanism of action

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones that regulate blood glucose levels and maintain glucose homeostasis. It is estimated that the activity of GLP-1 and GIP contribute more than 70% to the insulin response to an oral glucose challenge. They stimulate insulin secretion in a glucose-dependent manner via G-protein-coupled GIP and GLP-1 receptor signalling. In addition to their effects on insulin secretion, GLP-1 is also involved in promoting islet neogenesis and differentiation, as well as attenuating pancreatic beta-cell apoptosis. Incretin hormones also exert extra-pancreatic effects, such as lipogenesis and myocardial function. In type II diabetes mellitus, GLP-1 secretion is impaired, and the insulinotropic effect of GIP is significantly diminished. Vildagliptin exerts its blood glucose-lowering effects by selectively inhibiting dipeptidyl peptidase-4 (DPP-4), an enzyme that rapidly truncates and inactivates GLP-1 and GIP upon their release from the intestinal cells. DPP-4 cleaves oligopeptides after the second amino acid from the N-terminal end. Inhibition of DPP-4 substantially prolongs the half-life of GLP-1 and GIP, increasing the levels of active circulating incretin hormones. The duration of DPP-4 inhibition by vildagliptin is dose-dependent. Vildagliptin reduces fasting and prandial glucose and HbA1c. It enhances the glucose sensitivity of alpha- and beta-cells and augments glucose-dependent insulin secretion. Fasting and postprandial glucose levels are decreased, and postprandial lipid and lipoprotein metabolism are also improved.

Pharmacodynamics

Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control. In clinical trials, treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta-cells, proinsulin to insulin ratio, and measures of beta-cell responsiveness from the frequently-sampled meal tolerance test. Vildagliptin has improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels.