SAXENDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SAXENDA (SAXENDA).
Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases insulin secretion, decreases glucagon secretion, delays gastric emptying, and promotes satiety via central GLP-1 receptor activation.
| Metabolism | Metabolized via endogenous peptidases (similar to large proteins); no specific CYP450 enzyme involvement. Elimination half-life is approximately 13 hours. |
| Excretion | Renal excretion of intact liraglutide is minimal; approximately 6% is excreted as intact liraglutide in urine. The remainder is metabolized and eliminated via the kidneys and feces, with no single metabolite accounting for >10% of the dose. |
| Half-life | 11–13 hours (subcutaneous). Steady-state is reached after 3–5 once-daily doses. |
| Protein binding | >99%, primarily to albumin and other plasma proteins. |
| Volume of Distribution | 0.07 L/kg (mean after subcutaneous administration). This low Vd indicates limited distribution into tissues, consistent with high protein binding. |
| Bioavailability | Subcutaneous: approximately 55%. |
| Onset of Action | Subcutaneous: Blood glucose reduction begins within 1–2 hours after injection; peak gastric emptying delay occurs within 2–3 hours. |
| Duration of Action | Subcutaneous: The glucose-lowering effect lasts approximately 24 hours, supporting once-daily dosing. Gastric emptying delay persists for about 4–6 hours post-dose. |
Subcutaneous injection once daily, starting at 0.6 mg and titrating weekly by 0.6 mg increments to a maintenance dose of 3.0 mg.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). For severe renal impairment (eGFR <30 mL/min) or end-stage renal disease, use is not recommended. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, use is not recommended. |
| Pediatric use | Not approved for use in pediatric patients (age <18 years). Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment recommended, but caution due to age-related renal impairment and limited clinical experience in patients ≥75 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SAXENDA (SAXENDA).
| Breastfeeding | It is not known whether liraglutide is excreted in human breast milk. In lactating rats, liraglutide was detected in milk at approximately 3-4% of maternal plasma concentration (a proxy M/P ratio of 0.03-0.04). However, due to limited human data and potential for adverse effects in nursing infants (e.g., gastrointestinal effects, risk of hypoglycemia), breastfeeding is not recommended during treatment with SAXENDA. If unavoidable, monitor infant for signs of hypoglycemia and gastrointestinal distress. |
| Teratogenic Risk | Based on animal studies, liraglutide (SAXENDA) has shown fetal toxicity and teratogenic effects at clinically relevant exposures. Studies in rats and rabbits noted decreased fetal weight, increased incidence of fetal abnormalities (e.g., skeletal and visceral malformations) at maternal exposures similar to human exposure at the maximum recommended dose. In rats, structural abnormalities including reduced heart size, delayed ossification, and fetal loss were observed. Due to the lack of adequate human data and the potential for teratogenicity, use is contraindicated during pregnancy. Risk cannot be excluded; first trimester exposure may pose the highest risk for major malformations. |
■ FDA Black Box Warning
Risk of thyroid C-cell tumors: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rodents. It is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with 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)","Hypersensitivity to liraglutide or any product components","Pregnancy (discontinue if pregnancy occurs)"]
| Precautions | ["Risk of acute pancreatitis (discontinue if suspected)","Risk of gallbladder disease (cholelithiasis, cholecystitis)","Risk of hypoglycemia when used with insulin or sulfonylureas","Heart rate increase (monitor in patients with cardiac disease)","Renal impairment (acute kidney injury reported, especially with volume depletion)","Suicidal behavior and ideation (monitor for depression)","Hypersensitivity reactions (angioedema, anaphylaxis)"] |
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| Fetal Monitoring | No specific fetal monitoring is routinely recommended, but pregnancy testing should be performed prior to initiation in women of childbearing potential. If a patient becomes pregnant during therapy, SAXENDA should be discontinued immediately. For women exposed during pregnancy, consider referral to a maternal-fetal medicine specialist for detailed fetal ultrasound to assess for congenital anomalies. Monitor maternal weight and metabolic control (e.g., HbA1c, blood glucose) as pregnancy progresses. |
| Fertility Effects | Animal studies have shown no adverse effects on male or female fertility in rats at exposures up to 10 times the human exposure. However, human data are lacking. SAXENDA is indicated for weight management; significant weight loss may improve fertility in some women with obesity, but no direct effect on fertility is established. As a precaution, women planning pregnancy should discontinue SAXENDA due to potential teratogenic risk. |