KOMBIGLYZE XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KOMBIGLYZE XR (KOMBIGLYZE XR).

How it works

KOMBIGLYZE XR is a combination of saxagliptin, a DPP-4 inhibitor, and metformin, an AMPK activator. Saxagliptin increases incretin levels (GLP-1, GIP) by inhibiting DPP-4, leading to increased insulin release and decreased glucagon secretion. Metformin decreases hepatic gluconeogenesis and increases peripheral insulin sensitivity.

What the body does with it

Metabolism	Saxagliptin is metabolized via CYP3A4/5 to an active metabolite. Metformin is not metabolized and is excreted unchanged in urine.
Excretion	Renal excretion of unchanged saxagliptin (24%) and its active metabolite 5-hydroxy saxagliptin (22%); fecal excretion of parent (0.3%) and metabolite (6%); total renal elimination accounts for approximately 75% of the administered dose.
Half-life	Terminal elimination half-life for saxagliptin is 2.5 hours and for its active metabolite is 3.1 hours; clinical context: no significant accumulation at steady state.
Protein binding	Saxagliptin is approximately 20% bound to plasma proteins; its active metabolite is approximately 30% bound.
Volume of Distribution	Volume of distribution (Vd/F) is approximately 1.0 L/kg for saxagliptin, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability of saxagliptin is approximately 75% (range 50-80%); not significantly affected by food.
Onset of Action	Peak plasma concentrations for saxagliptin achieved within 2 hours; clinical effect on postprandial glucose begins within 30 minutes after oral administration.
Duration of Action	Duration of DPP-4 inhibition >12 hours; supports once-daily dosing for glycemic control over 24 hours.

Classification & Brands

Brand Substitutes

Riax-M XR 5mg/1000mg Tablet

Dosing & administration

One tablet orally once daily with food; available strengths: saxagliptin 5 mg/metformin extended-release 500 mg, saxagliptin 5 mg/metformin extended-release 1000 mg. Titrate based on glycemic response and tolerability.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	Contraindicated if eGFR <30 mL/min/1.73 m². No dose adjustment required for eGFR ≥30 mL/min/1.73 m². Assess renal function prior to initiation and periodically.
Liver impairment	Not recommended for use in patients with hepatic impairment due to lack of data; use with caution in Child-Pugh class A, B, or C.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years.
Geriatric use	Initiate at low dose of metformin component (500 mg once daily); monitor renal function due to age-related decline; increased risk of lactic acidosis in elderly with reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KOMBIGLYZE XR (KOMBIGLYZE XR).

Breastfeeding	Metformin is excreted into human milk in low amounts (M/P ratio approximately 0.35); infant exposure estimated at 0.5-1% of maternal weight-adjusted dose. Saxagliptin excretion unknown; caution advised. Use only if clearly needed.
Teratogenic Risk	FDA Pregnancy Category B. First trimester: Animal studies did not demonstrate teratogenic effects for metformin or saxagliptin. Second and third trimesters: Limited human data; metformin crosses placenta but no increased risk of major congenital anomalies. Saxagliptin has insufficient human data; avoid unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Lactic acidosis: Metformin accumulation can cause lactic acidosis, which is fatal in ~50% of cases. Risk factors include renal impairment, hypoperfusion, sepsis, hepatic impairment, and alcohol abuse.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe renal impairment (eGFR < 30 mL/min/1.73 m²)","Acute or chronic metabolic acidosis (including diabetic ketoacidosis)","History of serious hypersensitivity reaction to saxagliptin or metformin"]

Clinical Precautions

Precautions

["Lactic acidosis risk","Pancreatitis","Heart failure (saxagliptin increases risk of hospitalization)","Renal impairment (monitor renal function)","Hypoglycemia when used with sulfonylureas or insulin","Vitamin B12 deficiency (long-term metformin use)","Hypersensitivity reactions"]

Clinical Tips & Counseling

Drug interactions

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KOMBIGLYZE XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KOMBIGLYZE XR (KOMBIGLYZE XR).

How it works

What the body does with it

Metabolism	Saxagliptin is metabolized via CYP3A4/5 to an active metabolite. Metformin is not metabolized and is excreted unchanged in urine.
Excretion	Renal excretion of unchanged saxagliptin (24%) and its active metabolite 5-hydroxy saxagliptin (22%); fecal excretion of parent (0.3%) and metabolite (6%); total renal elimination accounts for approximately 75% of the administered dose.
Half-life	Terminal elimination half-life for saxagliptin is 2.5 hours and for its active metabolite is 3.1 hours; clinical context: no significant accumulation at steady state.
Protein binding	Saxagliptin is approximately 20% bound to plasma proteins; its active metabolite is approximately 30% bound.
Volume of Distribution	Volume of distribution (Vd/F) is approximately 1.0 L/kg for saxagliptin, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability of saxagliptin is approximately 75% (range 50-80%); not significantly affected by food.
Onset of Action	Peak plasma concentrations for saxagliptin achieved within 2 hours; clinical effect on postprandial glucose begins within 30 minutes after oral administration.
Duration of Action	Duration of DPP-4 inhibition >12 hours; supports once-daily dosing for glycemic control over 24 hours.

Classification & Brands

Brand Substitutes

Riax-M XR 5mg/1000mg Tablet

Dosing & administration

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	Contraindicated if eGFR <30 mL/min/1.73 m². No dose adjustment required for eGFR ≥30 mL/min/1.73 m². Assess renal function prior to initiation and periodically.
Liver impairment	Not recommended for use in patients with hepatic impairment due to lack of data; use with caution in Child-Pugh class A, B, or C.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years.
Geriatric use	Initiate at low dose of metformin component (500 mg once daily); monitor renal function due to age-related decline; increased risk of lactic acidosis in elderly with reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KOMBIGLYZE XR (KOMBIGLYZE XR).

Breastfeeding	Metformin is excreted into human milk in low amounts (M/P ratio approximately 0.35); infant exposure estimated at 0.5-1% of maternal weight-adjusted dose. Saxagliptin excretion unknown; caution advised. Use only if clearly needed.
Teratogenic Risk	FDA Pregnancy Category B. First trimester: Animal studies did not demonstrate teratogenic effects for metformin or saxagliptin. Second and third trimesters: Limited human data; metformin crosses placenta but no increased risk of major congenital anomalies. Saxagliptin has insufficient human data; avoid unless benefit outweighs risk.