Sitagliptin

• Type 2 Diabetes
• Glycemic Control
• Blood Sugar Management

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to improve glycemic control in adults with type 2 diabetes mellitus. It was the first DPP-4 inhibitor approved in the United States and enhances the body's incretin system.

Mechanism of Action

Sitagliptin works by enhancing incretin hormone activity:

• DPP-4 inhibition: Prevents breakdown of GLP-1 and GIP (incretin hormones)
• Increases active incretin levels: ~2-3 fold increase in intact GLP-1 and GIP
• Glucose-dependent insulin secretion: Incretins stimulate insulin release only when glucose is elevated
• Suppresses glucagon: Reduces hepatic glucose production
• Preserves beta cell function: May slow progressive beta cell decline

The glucose-dependent action results in minimal hypoglycemia risk.

Available Formulations

Sitagliptin is available as film-coated tablets:

• 25 mg, 50 mg, 100 mg tablets

Also available in combination:

• Sitagliptin/metformin (Janumet, Janumet XR)

Medical Uses

FDA-Approved Indication:

• Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

May be used as monotherapy or in combination with metformin, sulfonylureas, thiazolidinediones, or insulin.

Dosing Guidelines

Adults:

• 100 mg once daily
• May be taken with or without food

Renal Impairment:

• eGFR ≥45 mL/min: 100 mg once daily
• eGFR 30-44 mL/min: 50 mg once daily
• eGFR <30 mL/min: 25 mg once daily
• ESRD requiring dialysis: 25 mg once daily; may give without regard to dialysis timing

Hepatic Impairment:

• Mild to moderate: No adjustment
• Severe: Not studied; use with caution

Important Safety Information

Warnings and Precautions:

• Pancreatitis: Cases of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, have been reported
• Heart failure: Observe for signs and symptoms of heart failure
• Hypersensitivity reactions: Anaphylaxis, angioedema, and severe cutaneous adverse reactions reported
• Severe and disabling arthralgia: May occur; discontinue if severe joint pain develops
• Bullous pemphigoid: Cases reported; discontinue if suspected
• Hypoglycemia with insulin/sulfonylureas: May require reduced doses

Contraindications:

• History of serious hypersensitivity reaction to sitagliptin

Drug Interactions

• Digoxin: Slight increase in digoxin levels; monitor
• Insulin and sulfonylureas: Increased hypoglycemia risk; consider dose reduction
• No CYP450 interactions: Sitagliptin has minimal effect on CYP enzymes

Special Populations

• Hepatic Impairment: No adjustment for mild to moderate
• Renal Impairment: Dose adjustment required based on eGFR
• Elderly: No adjustment needed; consider renal function
• Pregnancy: Limited data; not recommended (insulin preferred)
• Lactation: Unknown if excreted in milk
• Pediatric: Safety and efficacy not established