Sitazid

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years with type 2 diabetes mellitus:
• As monotherapy
• In combination with other antidiabetic agents including metformin, sulfonylureas, thiazolidinediones, insulin, or SGLT2 inhibitors when adequate glycemic control is not achieved with a single agent.

Important Off-label/Clinically Accepted Uses:

• Combination Therapy in Type 2 Diabetes with Cardiovascular Risk Factors:
  Used in practice for T2DM patients with mild cardiovascular disease where hypoglycemia needs to be minimized.
• Elderly Patients with Renal Impairment:
  Sitagliptin is preferred in older adults with declining renal function due to its favorable safety profile.

Route of Administration: Oral

Adults (≥18 years):

• Standard dose: 100 mg once daily, with or without food.
• Renal Impairment:
• eGFR ≥45 mL/min/1.73 m²: 100 mg once daily
• eGFR ≥30 to <45 mL/min/1.73 m²: 50 mg once daily
• eGFR <30 mL/min/1.73 m² (including ESRD on dialysis): 25 mg once daily

Pediatrics (10 to <18 years):

• Initial: 100 mg once daily
• Safety and efficacy in children <10 years not established.

Elderly:

• No dosage adjustment solely due to age. Renal function assessment is recommended before initiation.

Hepatic Impairment:

• No dosage adjustment necessary in mild to moderate impairment. Use caution in severe hepatic dysfunction due to limited data.

Treatment Duration:

• Long-term treatment; continue as long as glycemic control is not achieved and adverse events are not limiting.

Sitagliptin is a selective, competitive, and reversible inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). By inhibiting DPP-4, sitagliptin increases endogenous levels of active incretin hormones—primarily glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones enhance glucose-dependent insulin secretion and suppress glucagon release during hyperglycemia, thus improving glycemic control. Sitagliptin works only when blood glucose levels are elevated, thereby minimizing the risk of hypoglycemia.

• Absorption: Rapidly absorbed; peak plasma concentrations (Tmax) occur within 1–4 hours.
• Bioavailability: Approximately 87%; not affected by food.
• Distribution: Volume of distribution ~198 L; low plasma protein binding (~38%).
• Metabolism: Minimal metabolism (~16%); primarily via CYP3A4 and CYP2C8.
• Elimination: Primarily excreted unchanged in urine (87% via active tubular secretion).
• Half-life: Approximately 12.4 hours
• Excretion Route: Renal (mainly through OCT2 and MATE1 transporter systems)

Pregnancy:

• FDA Category: Previously Category B (now narrative-based).
• Animal studies show no fetal harm, but well-controlled human studies are lacking.
• Use only if clearly needed and potential benefit outweighs risk.

Lactation:

• Unknown if sitagliptin is excreted in human milk. Detected in rat milk.
• Consider the developmental and health benefits of breastfeeding along with maternal need for therapy.
• Caution advised; alternative therapies may be preferred for nursing mothers.

• Primary Class: Antidiabetic Agent
• Subclass: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor

• Known hypersensitivity to sitagliptin or any component of the formulation
• History of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema)
• Type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis (not effective in insulin-deficient states)

• Pancreatitis: Postmarketing reports of fatal and non-fatal pancreatitis. Discontinue if suspected.
• Hypoglycemia: Risk increases when used with insulin or sulfonylureas; dosage reduction may be necessary.
• Renal Impairment: Dose adjustment required; monitor renal function periodically.
• Heart Failure: Increased risk observed with other DPP-4 inhibitors; caution in patients with history of heart failure.
• Arthralgia: Severe disabling joint pain reported. Discontinue if symptoms occur.
• Hypersensitivity: Includes anaphylaxis, angioedema, Stevens-Johnson syndrome; discontinue permanently if hypersensitivity develops.

Common Adverse Effects (≥2%):

• Gastrointestinal: Nausea, abdominal pain
• Respiratory: Nasopharyngitis, upper respiratory tract infection
• Musculoskeletal: Headache, arthralgia
• Endocrine: Hypoglycemia (especially with sulfonylureas/insulin)

Serious Adverse Effects:

• Acute pancreatitis
• Hypersensitivity reactions (anaphylaxis, angioedema, SJS)
• Bullous pemphigoid
• Renal impairment (in patients with preexisting kidney disease)
• Severe disabling joint pain

Timing & Severity:

• Many mild effects occur within the first few weeks; serious effects are rare but may occur at any time during therapy.

• Digoxin: Slight increase in digoxin levels; monitor levels in high-risk patients.
• Sulfonylureas/Insulin: Increased risk of hypoglycemia; dose adjustment may be needed.
• Rifampin (CYP3A4 inducer): May decrease sitagliptin efficacy; monitor glycemic control.
• Enzyme Systems: Minor substrate of CYP3A4 and CYP2C8, but does not significantly induce or inhibit CYP enzymes.
• P-glycoprotein: Sitagliptin is a weak substrate; significant transporter-related interactions unlikely.

• FDA Safety Communication: Added risk of severe joint pain and bullous pemphigoid in DPP-4 class.
• ADA/EASD 2023 Guidelines: Sitagliptin remains a second-line therapy option for T2DM in patients without compelling indications for GLP-1 or SGLT2 inhibitors.
• Renal Impairment Guidance: Dosing table updated for patients with CKD stages 3–5 to avoid toxicity.
• No Recent Label Changes related to efficacy or newly approved indications.

• Store at: 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Humidity: Keep in a dry place; avoid exposure to moisture.
• Light: Store in original packaging to protect from light.
• Handling: Do not refrigerate or freeze. Keep tightly closed.
• Reconstitution: Not applicable (oral tablet)