LIRAGLUTIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).
Glucagon-like peptide-1 (GLP-1) receptor agonist; increases insulin secretion, decreases glucagon secretion, slows gastric emptying, and promotes satiety.
| 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. |
| Molecular Weight | 3756.2 |
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. |
| 1st trimester | Avoid: Liraglutide is not recommended during the first trimester due to potential risks; animal studies showed fetal toxicity at maternally toxic doses. Human data are insufficient. |
| 2nd trimester | Avoid: Limited human data; theoretical risk of fetal harm based on animal studies. Use only if clearly needed. |
| 3rd trimester | Avoid: Similar to second trimester; insufficient human data; potential for fetal effects. Alternative therapies preferred. |
Clinical note
Comprehensive clinical and safety monograph for LIRAGLUTIDE (LIRAGLUTIDE).
| Placental transfer | Liraglutide is a peptide with high molecular weight; placental transfer is expected to be minimal based on its structure, but no human data exist. Animal studies indicate exposure in fetal circulation. |
| Breastfeeding | Liraglutide is excreted in rat milk; unknown in human milk. Due to potential adverse effects on the nursing infant (e.g., gastrointestinal effects, thyroid C-cell tumors), breastfeeding is not recommended during treatment. Consider withdrawal of drug or discontinuing breastfeeding. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Monitor maternal blood glucose and HbA1c regularly. If exposed during pregnancy, fetal ultrasound to assess growth and anatomy. Neonates should be monitored for hypoglycemia. |
| Fertility Effects | Animal studies show reduced fertility, implantation failure, and delayed puberty at high doses; human data limited. Liraglutide may impair fertility in both males and females. |
■ 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).
| Serious Effects |
Personal or family history of medullary thyroid carcinoma (MTC)Multiple endocrine neoplasia syndrome type 2 (MEN 2)
| Precautions | Acute pancreatitis, Risk of hypoglycemia with insulin secretagogues, Acute kidney injury, Hypersensitivity reactions (e.g., anaphylaxis, angioedema), Heart rate increase, Cholelithiasis and cholecystitis |
| Food/Dietary | No specific food-drug interactions. Because liraglutide delays gastric emptying, high-fat meals may worsen nausea; advise low-fat meals during titration. Avoid excessive alcohol consumption as it may increase risk of pancreatitis. |
| Clinical Pearls | Liraglutide is a GLP-1 receptor agonist with a 13-hour half-life, allowing once-daily dosing. Titrate weekly from 0.6 mg to 1.8 mg for diabetes or up to 3.0 mg for weight management. Monitor for pancreatitis; discontinue if suspected. Contraindicated in patients with personal/family history of medullary thyroid carcinoma or MEN2. Use with caution in renal impairment (eGFR <30). Risk of hypoglycemia when combined with insulin or sulfonylureas; consider dose reduction of these agents. Gastrointestinal side effects (nausea, vomiting, diarrhea) are common; gradual titration mitigates these. Can delay gastric emptying, affecting absorption of oral medications. Effective for glycemic control and weight loss; also reduces cardiovascular risk in T2DM patients with established CVD. |
| Patient Advice | Inject liraglutide once daily at the same time, regardless of meals, subcutaneously in abdomen, thigh, or upper arm. · Start with 0.6 mg daily for one week, then increase by 0.6 mg weekly to target dose (max 1.8 mg for diabetes, 3.0 mg for weight loss). · If a dose is missed, skip it and take the next dose at the usual time; do not double up. · Common side effects include nausea, vomiting, diarrhea, and constipation; these often improve over time. Eat smaller, low-fat meals to reduce nausea. · Seek medical help immediately if you experience severe abdominal pain (possible pancreatitis) or a lump in the neck, hoarseness, or trouble swallowing (possible thyroid tumor). · Do not use if you or your family have had medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. · Monitor blood glucose regularly if using insulin or sulfonylureas; adjust doses as instructed to avoid low blood sugar. · This medication can cause weight loss; inform your doctor if unintended weight loss occurs. · Store in refrigerator; after first use, can be stored at room temperature for up to 30 days. |
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