Saxagliptin

• Type 2 Diabetes
• Glycemic Control
• Blood Sugar Management

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to improve glycemic control in adults with type 2 diabetes mellitus. It enhances the body's natural incretin system to regulate blood glucose levels.

Mechanism of Action

Saxagliptin works by enhancing incretin hormone activity:

• DPP-4 inhibition: Prevents breakdown of GLP-1 and GIP (incretin hormones)
• Increases active GLP-1 levels: 2-3 fold increase in intact incretin concentrations
• Glucose-dependent insulin secretion: GLP-1 stimulates insulin release only when glucose is elevated
• Glucagon suppression: Reduces hepatic glucose production
• Preservation of beta cell function: May slow progressive loss of beta cell function

The glucose-dependent action results in low hypoglycemia risk.

Available Formulations

Saxagliptin is available as film-coated tablets:

• 2.5 mg tablets
• 5 mg tablets

Also available in combination:

• Saxagliptin/metformin (Kombiglyze XR)
• Saxagliptin/dapagliflozin (Qtern)

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:

• 2.5 mg or 5 mg once daily
• May be taken with or without food

Renal Impairment:

• eGFR ≥45 mL/min: No adjustment needed
• eGFR <45 mL/min: 2.5 mg once daily
• ESRD requiring hemodialysis: 2.5 mg once daily; administer post-dialysis

With Strong CYP3A4/5 Inhibitors:

• 2.5 mg once daily

Important Safety Information

Warnings and Precautions:

• Heart failure: FDA required a cardiovascular outcomes trial (SAVOR-TIMI 53) which showed increased hospitalization for heart failure; use with caution in patients at risk
• Pancreatitis: Cases reported; discontinue if suspected
• Severe and disabling arthralgia: May occur; discontinue if severe joint pain develops
• Bullous pemphigoid: Rare cases reported; discontinue if suspected
• Hypoglycemia with insulin/sulfonylureas: Consider reducing doses of insulin or sulfonylureas

Contraindications:

• History of serious hypersensitivity reaction to saxagliptin

Drug Interactions

Strong CYP3A4/5 Inhibitors (ketoconazole, atazanavir, clarithromycin, ritonavir, nelfinavir):

• Reduce saxagliptin dose to 2.5 mg daily

CYP3A4/5 Inducers:

• May reduce saxagliptin efficacy; consider alternatives

Insulin and Sulfonylureas:

• May cause hypoglycemia; consider reducing their doses

Special Populations

• Hepatic Impairment: No adjustment needed for mild to moderate; not studied in severe
• Renal Impairment: Reduce to 2.5 mg daily if eGFR <45 mL/min
• Elderly: No dose adjustment; use with caution due to potential for decreased renal function
• Pregnancy: Limited data; not recommended (insulin preferred)
• Lactation: Unknown if excreted in milk
• Pediatric: Safety and efficacy not established