DAPAGLIFLOZIN AND SAXAGLIPTIN MONOHYDRATE

Clinical safety rating: safe

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

How it works

Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal glucose reabsorption, increasing urinary glucose excretion. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that prolongs incretin hormone activity, enhancing insulin secretion and decreasing glucagon release.

What the body does with it

Metabolism	Dapagliflozin: primarily metabolized via UGT1A9-glucuronidation, minor CYP-mediated metabolism (CYP3A4). Saxagliptin: extensively metabolized via CYP3A4/5 to active metabolite 5-hydroxy saxagliptin.
Excretion	Dapagliflozin: 75% renal (mainly as inactive glucuronide metabolite, 2% as parent drug), 21% fecal. Saxagliptin: 75% renal (metabolites, 24% as parent drug), 22% fecal. Biliary: negligible.
Half-life	Dapagliflozin: terminal half-life ~12.9 hours after oral dose, supporting once-daily dosing. Saxagliptin: terminal half-life ~2.5 hours for parent drug; its active metabolite has half-life ~3.1 hours; overall DPP-4 inhibition sustained for 24 hours.
Protein binding	Dapagliflozin: ~91% bound to plasma proteins, primarily albumin. Saxagliptin: negligible binding (<10%); active metabolite similarly low.
Volume of Distribution	Dapagliflozin: Vd ~118 L (1.5 L/kg) indicating extensive extravascular distribution. Saxagliptin: Vd ~1.7 L/kg, moderate tissue distribution.
Bioavailability	Dapagliflozin: oral bioavailability ~78%, unaffected by food. Saxagliptin: oral bioavailability ~67%, food slightly reduces rate but not extent.
Onset of Action	Oral: Dapagliflozin reduces renal glucose reabsorption within 1 hour; peak SGLT2 inhibition at 2-3 hours. Saxagliptin inhibits DPP-4 within 30 minutes; maximal glucose-lowering effect seen within 1-2 hours.
Duration of Action	Dapagliflozin: 24 hours (once-daily dosing) due to prolonged SGLT2 inhibition. Saxagliptin: 24 hours due to sustained DPP-4 inhibition despite shorter half-life, from active metabolite.

Classification & Brands

Dosing & administration

Oral, 5 mg dapagliflozin / 5 mg saxagliptin once daily, with or without food.

Dosage form	TABLET
Renal impairment	eGFR ≥45 mL/min/1.73 m²: no adjustment; eGFR 30–44 mL/min/1.73 m²: not recommended; eGFR <30 mL/min/1.73 m²: contraindicated.
Liver impairment	Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not recommended (has not been studied and saxagliptin exposure is increased in severe hepatic impairment).
Pediatric use	Not established; safety and efficacy not studied in pediatric patients.
Geriatric use	No specific dose adjustment based on age; monitor renal function due to age-related decline in GFR; consider lower starting doses in elderly patients if renal function is reduced according to renal adjustment guidelines.

Use during pregnancy

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	Dapagliflozin: Excreted in animal milk; unknown in humans. Saxagliptin: Excreted in animal milk; not recommended during breastfeeding. M/P ratio not established.
Teratogenic Risk	Dapagliflozin: Based on animal studies, may affect renal development; human data insufficient. Avoid in second and third trimesters due to potential risk of fetal renal impairment and oligohydramnios. Saxagliptin: Animal studies show no major teratogenicity; limited human data. Overall, avoid during pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Nasopharyngitis
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Severe renal impairment (eGFR <30 mL/min/1.73 m²)","History of serious hypersensitivity reaction to saxagliptin or dapagliflozin"]

Clinical Precautions

Precautions

["Pancreatitis","Ketoacidosis (including euglycemic ketoacidosis)","Acute kidney injury and renal impairment","Urosepsis and pyelonephritis","Hypoglycemia when used with insulin or sulfonylureas","Hypersensitivity reactions (e.g., anaphylaxis, angioedema)","Severe and disabling arthralgia","Heart failure with saxagliptin"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

DAPAGLIFLOZIN AND SAXAGLIPTIN MONOHYDRATE

Clinical safety rating: safe

Strong CYP3A4/5 inhibitors may increase levels May cause hypersensitivity reactions including anaphylaxis.

How it works

What the body does with it

Metabolism	Dapagliflozin: primarily metabolized via UGT1A9-glucuronidation, minor CYP-mediated metabolism (CYP3A4). Saxagliptin: extensively metabolized via CYP3A4/5 to active metabolite 5-hydroxy saxagliptin.
Excretion	Dapagliflozin: 75% renal (mainly as inactive glucuronide metabolite, 2% as parent drug), 21% fecal. Saxagliptin: 75% renal (metabolites, 24% as parent drug), 22% fecal. Biliary: negligible.
Half-life	Dapagliflozin: terminal half-life ~12.9 hours after oral dose, supporting once-daily dosing. Saxagliptin: terminal half-life ~2.5 hours for parent drug; its active metabolite has half-life ~3.1 hours; overall DPP-4 inhibition sustained for 24 hours.
Protein binding	Dapagliflozin: ~91% bound to plasma proteins, primarily albumin. Saxagliptin: negligible binding (<10%); active metabolite similarly low.
Volume of Distribution	Dapagliflozin: Vd ~118 L (1.5 L/kg) indicating extensive extravascular distribution. Saxagliptin: Vd ~1.7 L/kg, moderate tissue distribution.
Bioavailability	Dapagliflozin: oral bioavailability ~78%, unaffected by food. Saxagliptin: oral bioavailability ~67%, food slightly reduces rate but not extent.
Onset of Action	Oral: Dapagliflozin reduces renal glucose reabsorption within 1 hour; peak SGLT2 inhibition at 2-3 hours. Saxagliptin inhibits DPP-4 within 30 minutes; maximal glucose-lowering effect seen within 1-2 hours.
Duration of Action	Dapagliflozin: 24 hours (once-daily dosing) due to prolonged SGLT2 inhibition. Saxagliptin: 24 hours due to sustained DPP-4 inhibition despite shorter half-life, from active metabolite.

Classification & Brands

Dosing & administration

Oral, 5 mg dapagliflozin / 5 mg saxagliptin once daily, with or without food.

Dosage form	TABLET
Renal impairment	eGFR ≥45 mL/min/1.73 m²: no adjustment; eGFR 30–44 mL/min/1.73 m²: not recommended; eGFR <30 mL/min/1.73 m²: contraindicated.
Liver impairment	Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not recommended (has not been studied and saxagliptin exposure is increased in severe hepatic impairment).
Pediatric use	Not established; safety and efficacy not studied in pediatric patients.
Geriatric use	No specific dose adjustment based on age; monitor renal function due to age-related decline in GFR; consider lower starting doses in elderly patients if renal function is reduced according to renal adjustment guidelines.

Use during pregnancy

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	Dapagliflozin: Excreted in animal milk; unknown in humans. Saxagliptin: Excreted in animal milk; not recommended during breastfeeding. M/P ratio not established.
Teratogenic Risk	Dapagliflozin: Based on animal studies, may affect renal development; human data insufficient. Avoid in second and third trimesters due to potential risk of fetal renal impairment and oligohydramnios. Saxagliptin: Animal studies show no major teratogenicity; limited human data. Overall, avoid during pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Nasopharyngitis
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Severe renal impairment (eGFR <30 mL/min/1.73 m²)","History of serious hypersensitivity reaction to saxagliptin or dapagliflozin"]