SAXAGLIPTIN;METFORMIN HYDROCHLORIDE
Clinical safety rating: safe
Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.
Saxagliptin inhibits DPP-4, increasing incretin levels (GLP-1, GIP), enhancing glucose-dependent insulin secretion and reducing glucagon. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
| Metabolism | Saxagliptin: CYP3A4/3A5 (major); Metformin: Not metabolized, excreted unchanged in urine. |
| Excretion | Saxagliptin: 75% renal (24% unchanged, 51% as metabolite), 22% fecal. Metformin: 90% renal (unchanged). |
| Half-life | Saxagliptin: 2.5 hours (parent), 3.1 hours (active metabolite). Metformin: 6.2 hours (plasma), prolonged in renal impairment. |
| Protein binding | Saxagliptin: Negligible (<10%). Metformin: Negligible (≤5%). |
| Volume of Distribution | Saxagliptin: 0.3-0.5 L/kg (moderate tissue distribution). Metformin: 0.8-1.0 L/kg (extensive distribution into erythrocytes and tissues). |
| Bioavailability | Saxagliptin: 75% (oral). Metformin: 50-60% (oral, immediate-release); 30-50% (extended-release). |
| Onset of Action | Saxagliptin/Metformin: Onset of glucose lowering within 1-2 hours; maximal effect at 2-4 weeks. |
| Duration of Action | Saxagliptin: 24 hours (once-daily dosing). Metformin: 8-12 hours (immediate-release), 24 hours (extended-release). Clinical effect persists with regular dosing. |
Each tablet contains saxagliptin 5 mg and metformin hydrochloride 500 mg or 1000 mg. The recommended starting dose is 5 mg saxagliptin and 500 mg metformin hydrochloride orally twice daily; titrate gradually based on efficacy and tolerability. Maximum daily dose: saxagliptin 5 mg, metformin hydrochloride 2000 mg.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated if eGFR <30 mL/min/1.73 m². If eGFR is 30-45 mL/min/1.73 m², limit metformin dose to 1000 mg/day; saxagliptin dose remains 5 mg/day (but note saxagliptin is not recommended in this range). Do not initiate if eGFR is 30-45 mL/min/1.73 m². Assess renal function before initiation and at least annually; more frequent monitoring if eGFR <60 mL/min/1.73 m². |
| Liver impairment | Avoid use in patients with hepatic impairment (Child-Pugh class A, B, or C) due to metformin component (risk of lactic acidosis). No specific dose adjustment for saxagliptin alone, but combination not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | Initiate at lowest dose (2.5 mg saxagliptin; 500 mg metformin) and titrate slowly. Use with caution due to age-related decline in renal function; monitor renal function closely. Avoid if eGFR <30 mL/min/1.73 m². Risk of lactic acidosis increases with age due to metformin accumulation. |
| 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.
| FDA category | Animal |
| Breastfeeding | Saxagliptin: Unknown if excreted in human milk; risk cannot be excluded. Metformin: Excreted in breast milk in low amounts; M/P ratio approximately 0.1–0.4. Consider benefits of breastfeeding vs. potential adverse effects; caution advised. |
| Teratogenic Risk | Pregnancy Category X. Saxagliptin: Limited human data; animal studies show no major malformations but fetal toxicity at high doses. Metformin: Not associated with increased risk of major birth defects; however, poor glycemic control increases fetal risks. Use contraindicated in pregnancy, especially second and third trimesters, due to risk of neonatal hypoglycemia and potential for metformin-induced lactic acidosis in mother. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Nasopharyngitis |
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73m²) (metformin)","Acute or chronic metabolic acidosis (including diabetic ketoacidosis) (metformin)","History of serious hypersensitivity reaction to saxagliptin or metformin (e.g., anaphylaxis, angioedema)"]
| Precautions | ["Lactic acidosis (metformin accumulation; risk factors: renal impairment, acute decompensated heart failure, age ≥65, hepatic impairment, excessive alcohol, surgery, hypoxic states)","Pancreatitis (saxagliptin; has been reported postmarketing)","Heart failure (saxagliptin; consider risks in patients with known CV disease)","Severe and disabling arthralgia (saxagliptin)","Hypoglycemia when combined with insulin secretagogues or insulin","Renal impairment (metformin; contraindicated if eGFR <30 mL/min/1.73m²)"] |
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| Fetal Monitoring | Monitor maternal blood glucose, hemoglobin A1c, renal function (serum creatinine, eGFR), and hepatic function. Assess fetal growth and well-being via ultrasound, especially if hyperglycemia uncontrolled. Monitor for signs of lactic acidosis in mother (dyspnea, abdominal pain, hypothermia). |
| Fertility Effects | Saxagliptin: No significant adverse effects on fertility in animal studies. Metformin may improve fertility in women with PCOS by reducing hyperinsulinemia and restoring ovulation. However, use during pregnancy is not recommended. |