SAXAGLIPTIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), which prolongs the action of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thereby enhancing glucose-dependent insulin secretion and suppressing glucagon release.
| Metabolism | Metabolized primarily via cytochrome P450 3A4/5 (CYP3A4/5) to an active metabolite (5-hydroxy saxagliptin). Approximately 75% of the dose is excreted in urine (as unchanged drug and metabolites) and 22% in feces. |
| Excretion | Renal (75% as unchanged drug and metabolites; 25% as unchanged drug in urine) and fecal (22% as metabolites). |
| Half-life | Terminal half-life: 2.5 hours; accounts for DPP-4 inhibition duration despite rapid clearance. |
| Protein binding | Negligible (<10%); primarily to albumin. |
| Volume of Distribution | Approximately 0.27 L/kg (total ~0.73 L/kg); indicates distribution primarily in extracellular fluid. |
| Bioavailability | Oral: Approximately 67% (high bioavailability due to minimal first-pass metabolism). |
| Onset of Action | Oral: 0.5–1 hour to achieve peak plasma concentration; DPP-4 inhibition occurs within 30 minutes. |
| Duration of Action | DPP-4 inhibition >80% sustained for 24 hours; clinical effect on glucose lasts 24 hours with once-daily dosing. |
2.5 mg or 5 mg orally once daily irrespective of meals.
| Dosage form | TABLET |
| Renal impairment | For eGFR <45 mL/min/1.73 m2 (CKD stage 3b, 4, or ESRD): 2.5 mg once daily. No adjustment for eGFR ≥45 mL/min/1.73 m2. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no dose adjustment. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Not approved for pediatric patients; efficacy and safety not established. |
| Geriatric use | No specific dose adjustment required based on age alone; consider renal function and potential for increased hypoglycemia risk when used with sulfonylureas or insulin. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.
| Breastfeeding | No human data; saxagliptin is excreted in rat milk (M/P ratio ~1:1). Potential for serious adverse effects in nursing infants; discontinue breastfeeding or drug, considering importance of drug to mother. |
| Teratogenic Risk | FDA Pregnancy Category X. In animal studies, saxagliptin caused adverse fetal effects (e.g., reduced fetal weight, minor skeletal variations) at exposures 2- to 4-fold the human AUC at the MRHD. No adequate human studies; known risk of congenital malformations based on animal data. Use contraindicated in all trimesters. |
■ FDA Black Box Warning
Saxagliptin is not recommended for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
| Common Effects | Nasopharyngitis |
| Serious Effects |
["History of serious hypersensitivity reaction to saxagliptin (e.g., anaphylaxis, angioedema)","Type 1 diabetes mellitus","Diabetic ketoacidosis"]
| Precautions | ["Pancreatitis (including fatal cases) has been reported; monitor for signs and symptoms","Risk of heart failure in patients with established cardiovascular disease or renal impairment","Arthralgia, severe and disabling","Bullous pemphigoid requiring hospitalization","Hypoglycemia when used in combination with sulfonylurea or insulin","Macrovascular outcomes: no conclusive evidence of reduced risk"] |
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| Fetal Monitoring | Monitor maternal blood glucose, HbA1c, and renal function. Fetal monitoring: serial ultrasound for growth and anatomy. No specific antidote; discontinue immediately if pregnancy detected. |
| Fertility Effects | No human fertility data; in animal studies, no adverse effects on mating, fertility, or early embryonic development at exposures up to 2-fold MRHD. |