LIRAGLUTIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).

How it works

Glucagon-like peptide-1 (GLP-1) receptor agonist; increases insulin secretion, decreases glucagon secretion, slows gastric emptying, and promotes satiety.

What the body does with it

Metabolism	Degraded by endogenous peptidases (DPP-4 and neutral endopeptidases); no CYP450 involvement; metabolites are inactive.
Excretion	Liraglutide is primarily eliminated via degradation into smaller peptides and amino acids, with no significant renal or biliary excretion of the intact drug. Approximately 6% of the dose is excreted unchanged in urine, and less than 5% is excreted in feces as intact liraglutide.
Half-life	The terminal elimination half-life of liraglutide after subcutaneous administration is approximately 13 hours, supporting once-daily dosing. The prolonged half-life is due to albumin binding and reduced renal clearance.
Protein binding	Liraglutide is >98% bound to plasma proteins, primarily albumin. This high binding contributes to its long half-life.
Volume of Distribution	The volume of distribution after subcutaneous administration is approximately 0.07 L/kg, indicating limited extravascular distribution and primarily remaining in the circulation.
Bioavailability	Subcutaneous: Absolute bioavailability is approximately 55% (range 46-64%). Oral bioavailability is negligible (<1%) due to enzymatic degradation in the gastrointestinal tract.
Onset of Action	Subcutaneous: Onset of clinical effect (glucose lowering) occurs within 2-4 hours after a single dose, with peak effect at 8-12 hours.
Duration of Action	Subcutaneous: The glucose-lowering effect persists for approximately 24 hours with once-daily dosing, allowing consistent glycemic control throughout the day. The extended duration is due to slow absorption and albumin binding.

Classification & Brands

Dosing & administration

Liraglutide is administered subcutaneously once daily. For type 2 diabetes, start at 0.6 mg daily for one week, then increase to 1.2 mg daily; may further increase to 1.8 mg daily if needed. For weight management (with BMI ≥30 or ≥27 with comorbidities), start at 0.6 mg daily for one week, then escalate weekly by 0.6 mg to a target dose of 3.0 mg daily.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild renal impairment (eGFR ≥60 mL/min/1.73 m²). For moderate impairment (eGFR 30-59), use with caution; limited data. Contraindicated in end-stage renal disease (eGFR <15). No experience in severe impairment (eGFR 15-29); use not recommended.
Liver impairment	No dose adjustment needed for mild hepatic impairment (Child-Pugh class A). Not recommended for moderate to severe hepatic impairment (Child-Pugh class B or C) due to lack of data.
Pediatric use	Not approved for pediatric patients under 18 years of age for either type 2 diabetes or weight management.
Geriatric use	No dose adjustment based solely on age. Caution in patients ≥75 years due to limited therapeutic experience; monitor renal function and gastrointestinal tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).

Breastfeeding	Liraglutide is excreted in rat milk at a 3-11% ratio relative to maternal plasma; human data unavailable. Not recommended during breastfeeding due to unknown risks to the infant. M/P ratio not determined in humans.
Teratogenic Risk	Liraglutide is contraindicated in pregnancy. Based on animal studies, it may cause fetal harm. First trimester: avoid use due to potential for malformations. Second and third trimesters: not recommended due to risks of fetal growth restriction and other adverse outcomes.

Warnings & precautions

■ FDA Black Box Warning

Risk of thyroid C-cell tumors; contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Side Effect Profile

Serious Effects

Absolute Contraindications

["Personal or family history of medullary thyroid carcinoma","Multiple Endocrine Neoplasia syndrome type 2","Hypersensitivity to liraglutide or any product components"]

Clinical Precautions

Precautions

["Acute pancreatitis","Risk of hypoglycemia with insulin secretagogues","Acute kidney injury","Hypersensitivity reactions (e.g., anaphylaxis, angioedema)","Heart rate increase","Cholelithiasis and cholecystitis"]

Clinical Tips & Counseling

Drug interactions

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LIRAGLUTIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).

How it works

Glucagon-like peptide-1 (GLP-1) receptor agonist; increases insulin secretion, decreases glucagon secretion, slows gastric emptying, and promotes satiety.

What the body does with it

Metabolism	Degraded by endogenous peptidases (DPP-4 and neutral endopeptidases); no CYP450 involvement; metabolites are inactive.
Excretion	Liraglutide is primarily eliminated via degradation into smaller peptides and amino acids, with no significant renal or biliary excretion of the intact drug. Approximately 6% of the dose is excreted unchanged in urine, and less than 5% is excreted in feces as intact liraglutide.
Half-life	The terminal elimination half-life of liraglutide after subcutaneous administration is approximately 13 hours, supporting once-daily dosing. The prolonged half-life is due to albumin binding and reduced renal clearance.
Protein binding	Liraglutide is >98% bound to plasma proteins, primarily albumin. This high binding contributes to its long half-life.
Volume of Distribution	The volume of distribution after subcutaneous administration is approximately 0.07 L/kg, indicating limited extravascular distribution and primarily remaining in the circulation.
Bioavailability	Subcutaneous: Absolute bioavailability is approximately 55% (range 46-64%). Oral bioavailability is negligible (<1%) due to enzymatic degradation in the gastrointestinal tract.
Onset of Action	Subcutaneous: Onset of clinical effect (glucose lowering) occurs within 2-4 hours after a single dose, with peak effect at 8-12 hours.
Duration of Action	Subcutaneous: The glucose-lowering effect persists for approximately 24 hours with once-daily dosing, allowing consistent glycemic control throughout the day. The extended duration is due to slow absorption and albumin binding.

Classification & Brands

Dosing & administration

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild renal impairment (eGFR ≥60 mL/min/1.73 m²). For moderate impairment (eGFR 30-59), use with caution; limited data. Contraindicated in end-stage renal disease (eGFR <15). No experience in severe impairment (eGFR 15-29); use not recommended.
Liver impairment	No dose adjustment needed for mild hepatic impairment (Child-Pugh class A). Not recommended for moderate to severe hepatic impairment (Child-Pugh class B or C) due to lack of data.
Pediatric use	Not approved for pediatric patients under 18 years of age for either type 2 diabetes or weight management.
Geriatric use	No dose adjustment based solely on age. Caution in patients ≥75 years due to limited therapeutic experience; monitor renal function and gastrointestinal tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).

Breastfeeding	Liraglutide is excreted in rat milk at a 3-11% ratio relative to maternal plasma; human data unavailable. Not recommended during breastfeeding due to unknown risks to the infant. M/P ratio not determined in humans.
Teratogenic Risk	Liraglutide is contraindicated in pregnancy. Based on animal studies, it may cause fetal harm. First trimester: avoid use due to potential for malformations. Second and third trimesters: not recommended due to risks of fetal growth restriction and other adverse outcomes.

Warnings & precautions

■ FDA Black Box Warning

Risk of thyroid C-cell tumors; contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Side Effect Profile

Serious Effects

Absolute Contraindications

["Personal or family history of medullary thyroid carcinoma","Multiple Endocrine Neoplasia syndrome type 2","Hypersensitivity to liraglutide or any product components"]