STEGLATRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STEGLATRO (STEGLATRO).

How it works

Steglatro (ertugliflozin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It inhibits SGLT2 in the proximal renal tubule, reducing glucose reabsorption and increasing urinary glucose excretion, thereby lowering blood glucose.

What the body does with it

Metabolism	Ertugliflozin is primarily metabolized via glucuronidation by UGT1A9 and UGT2B7 to two inactive glucuronide metabolites. Minor metabolism via CYP3A4 and CYP2C8.
Excretion	Approximately 65% of the dose is excreted in the urine as unchanged drug via active tubular secretion, and 35% is excreted in the feces as unchanged drug, indicating minimal metabolism.
Half-life	Terminal elimination half-life is approximately 12.4 hours in patients with type 2 diabetes, supporting once-daily dosing. No accumulation occurs at steady state.
Protein binding	Approximately 95% bound to plasma proteins, primarily serum albumin.
Volume of Distribution	Mean apparent volume of distribution at steady state is 1.8 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 75% under fasted conditions. Absorption is not significantly affected by food, so it can be taken with or without meals.
Onset of Action	Oral administration: Onset of SGLT2 inhibition occurs within 1 hour, with maximal urinary glucose excretion observed at 24 hours after the first dose.
Duration of Action	The effect on urinary glucose excretion persists for 24 hours, allowing once-daily dosing. Continuous use leads to sustained reduction in HbA1c and body weight.

Classification & Brands

Dosing & administration

0.5 mg orally once daily for patients with type 2 diabetes; no dose adjustment for age, gender, or race.

Dosage form	TABLET
Renal impairment	eGFR ≥ 60 mL/min/1.73 m²: no dose adjustment. eGFR 30 to < 60: not recommended due to lack of efficacy. eGFR < 30: contraindicated.
Liver impairment	Child-Pugh Class A (mild): no dose adjustment. Child-Pugh Class B (moderate): not recommended. Child-Pugh Class C (severe): contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years.
Geriatric use	No dose adjustment required based solely on age. Consider renal function and risk of volume depletion.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for STEGLATRO (STEGLATRO).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or effects on milk production. Excreted in rat milk at concentrations 0.5-1.5 times maternal plasma. Due to potential for serious adverse reactions, advise against breastfeeding during treatment and for 2 weeks after last dose.
Teratogenic Risk	Pregnancy Category C: No adequate studies in pregnant women. In animal studies, fetal skeletal variations and reduced fetal weight were observed at exposures ≥1.8 times the human exposure at maximum recommended human dose. Use only if potential benefit justifies potential risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to ertugliflozin or any excipient","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease","On dialysis"]

Clinical Precautions

Precautions

["Risk of volume depletion and hypotension","Risk of acute kidney injury","Risk of urosepsis and pyelonephritis","Risk of hypoglycemia when used with insulin or insulin secretagogues","Risk of ketoacidosis (including euglycemic ketoacidosis)","Risk of necrotizing fasciitis of the perineum (Fournier gangrene)","Lower limb amputation risk","Increased LDL-C"]

Clinical Tips & Counseling

Drug interactions

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STEGLATRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STEGLATRO (STEGLATRO).

How it works

What the body does with it

Metabolism	Ertugliflozin is primarily metabolized via glucuronidation by UGT1A9 and UGT2B7 to two inactive glucuronide metabolites. Minor metabolism via CYP3A4 and CYP2C8.
Excretion	Approximately 65% of the dose is excreted in the urine as unchanged drug via active tubular secretion, and 35% is excreted in the feces as unchanged drug, indicating minimal metabolism.
Half-life	Terminal elimination half-life is approximately 12.4 hours in patients with type 2 diabetes, supporting once-daily dosing. No accumulation occurs at steady state.
Protein binding	Approximately 95% bound to plasma proteins, primarily serum albumin.
Volume of Distribution	Mean apparent volume of distribution at steady state is 1.8 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 75% under fasted conditions. Absorption is not significantly affected by food, so it can be taken with or without meals.
Onset of Action	Oral administration: Onset of SGLT2 inhibition occurs within 1 hour, with maximal urinary glucose excretion observed at 24 hours after the first dose.
Duration of Action	The effect on urinary glucose excretion persists for 24 hours, allowing once-daily dosing. Continuous use leads to sustained reduction in HbA1c and body weight.

Classification & Brands

Dosing & administration

0.5 mg orally once daily for patients with type 2 diabetes; no dose adjustment for age, gender, or race.

Dosage form	TABLET
Renal impairment	eGFR ≥ 60 mL/min/1.73 m²: no dose adjustment. eGFR 30 to < 60: not recommended due to lack of efficacy. eGFR < 30: contraindicated.
Liver impairment	Child-Pugh Class A (mild): no dose adjustment. Child-Pugh Class B (moderate): not recommended. Child-Pugh Class C (severe): contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years.
Geriatric use	No dose adjustment required based solely on age. Consider renal function and risk of volume depletion.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for STEGLATRO (STEGLATRO).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or effects on milk production. Excreted in rat milk at concentrations 0.5-1.5 times maternal plasma. Due to potential for serious adverse reactions, advise against breastfeeding during treatment and for 2 weeks after last dose.
Teratogenic Risk	Pregnancy Category C: No adequate studies in pregnant women. In animal studies, fetal skeletal variations and reduced fetal weight were observed at exposures ≥1.8 times the human exposure at maximum recommended human dose. Use only if potential benefit justifies potential risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to ertugliflozin or any excipient","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease","On dialysis"]