Trelagliptin Succinate

• Type 2 Diabetes Mellitus:
  Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Monotherapy or Combination Therapy:
  Used as monotherapy in patients inadequately controlled by diet and exercise alone or as add-on therapy to other antidiabetic agents (excluding insulin).
• Off-label Uses:
  Not widely used off-label; investigational in some combination regimens for type 2 diabetes management.

• Route: Oral tablets.
• Recommended Dose: 50 mg once weekly, orally, with or without food.
• Special Populations:
• Renal Impairment: No dose adjustment required for mild to moderate renal impairment. Use caution and consider dose adjustment or avoidance in severe renal impairment or end-stage renal disease.
• Hepatic Impairment: No dose adjustment needed for mild or moderate hepatic impairment; data limited for severe impairment.
• Elderly: No specific dose adjustment; monitor for hypoglycemia and renal function.
• Pediatrics: Safety and efficacy not established.

Trelagliptin is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. By inhibiting DPP-4 enzyme activity, trelagliptin prolongs the activity of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This enhances glucose-dependent insulin secretion and suppresses glucagon release, resulting in improved glycemic control by reducing fasting and postprandial blood glucose levels.

• Absorption: Rapidly absorbed with peak plasma concentrations (Cmax) reached within 1 to 2 hours after oral administration.
• Bioavailability: Approximately 90%.
• Distribution: Volume of distribution approximates 70 liters, indicating moderate tissue distribution.
• Metabolism: Minimal metabolism; primarily excreted unchanged.
• Half-life: Long elimination half-life (~75 hours), supporting once-weekly dosing.
• Elimination: Primarily excreted unchanged in urine (approximately 60%) and feces (approximately 40%).

• Pregnancy: Limited data in humans; animal studies show no direct teratogenic effects. Use only if benefits outweigh risks.
• Lactation: Unknown if excreted in human milk; caution advised. Breastfeeding not recommended during treatment.

• Oral antidiabetic agent
• Dipeptidyl peptidase-4 (DPP-4) inhibitor
• Gliptin class

• Known hypersensitivity to trelagliptin or any component of the formulation.
• Patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

• Monitor for signs of pancreatitis; discontinue if suspected.
• Use with caution in patients with renal impairment; monitor renal function regularly.
• Risk of hypersensitivity reactions, including angioedema and anaphylaxis.
• Caution in patients with history of heart failure; monitor symptoms.
• Monitor for joint pain; severe cases may require drug discontinuation.

• Common: Nasopharyngitis, headache, gastrointestinal discomfort, mild hypoglycemia (especially with concomitant sulfonylureas or insulin).
• Less Common: Pancreatitis, hypersensitivity reactions, rash, elevated liver enzymes.
• Rare: Severe joint pain, angioedema, anaphylactic reactions.

• No significant interactions with cytochrome P450 enzymes; minimal drug-drug interaction potential.
• Caution when used with insulin or sulfonylureas due to increased hypoglycemia risk.
• No significant interactions with food or alcohol reported.

• Approved as a once-weekly DPP-4 inhibitor option, providing convenience over daily DPP-4 inhibitors.
• Current diabetes management guidelines recognize DPP-4 inhibitors as second-line or add-on agents after metformin.
• Ongoing studies evaluating cardiovascular safety profile continue; current data suggest neutral effects on cardiovascular outcomes.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• No special reconstitution or refrigeration required.