SEMAGLUTIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEMAGLUTIDE (SEMAGLUTIDE).

How it works

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases insulin secretion, decreases glucagon secretion, slows gastric emptying, and reduces appetite and food intake.

What the body does with it

Metabolism	Semaglutide is metabolized via proteolytic cleavage of the peptide backbone and sequential beta-elimination of the C-terminal dipeptide. It is not primarily metabolized by CYP enzymes.
Excretion	Renal: 0%; Biliary/Fecal: ~97% as parent and metabolites; Urine: <3% as metabolites
Half-life	Terminal elimination half-life: ~1 week (168 hours) due to extensive plasma protein binding and reduced renal clearance, supporting once-weekly dosing
Protein binding	>99% bound to albumin
Volume of Distribution	Approximately 12.5 L (0.16 L/kg for a 75 kg patient), indicating limited extravascular distribution
Bioavailability	Subcutaneous: ~89%
Onset of Action	Subcutaneous: Glycemic effects begin within 2-4 weeks; significant HbA1c reduction observed by 8-12 weeks
Duration of Action	Subcutaneous: Weekly dosing maintains therapeutic concentrations for 7 days; clinical effects persist for up to 14 days after last dose due to long half-life

Classification & Brands

Dosing & administration

Subcutaneous injection once weekly, starting at 0.25 mg for 4 weeks, then 0.5 mg for 4 weeks, then may increase to 1 mg, 1.7 mg, or 2.4 mg based on glycemic response and tolerability.

Dosage form	INJECTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR >=30 mL/min/1.73 m2). Limited data in severe renal impairment (eGFR <30 mL/min/1.73 m2); use with caution due to increased exposure and gastrointestinal adverse effects. Not recommended in end-stage renal disease.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution.
Pediatric use	Not approved for patients <18 years of age. Safety and efficacy not established.
Geriatric use	No dose adjustment required based on age alone. Monitor renal function and tolerability, as elderly patients may be more sensitive to gastrointestinal effects and 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 SEMAGLUTIDE (SEMAGLUTIDE).

Breastfeeding	No human data; drug is excreted in rat milk. M/P ratio unknown. Theoretical risk of adverse effects in infant due to GLP-1 receptor agonism. Because of high molecular weight, significant transfer is unlikely, but caution advised.
Teratogenic Risk	First trimester: Limited human data; animal studies show embryotoxicity and malformations at high doses. Second and third trimesters: No adequate human studies; potential fetal harm due to maternal weight loss and nutritional deficiencies. GLP-1 receptor agonists may cause fetal growth restriction.

Warnings & precautions

■ FDA Black Box Warning

There is no FDA-issued boxed warning for semaglutide.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Personal or family history of medullary thyroid carcinoma","Multiple endocrine neoplasia syndrome type 2","Hypersensitivity to semaglutide or any components","Pregnancy (due to weight loss risks)"]

Clinical Precautions

Precautions

["Risk of thyroid C-cell tumors (observed in rodents, clinical relevance unknown)","Acute pancreatitis","Diabetic retinopathy complications (especially with rapid glucose lowering)","Hypoglycemia (when used with insulin or sulfonylureas)","Acute kidney injury or worsening of chronic kidney disease","Gallbladder disease (cholelithiasis, cholecystitis)","Gastrointestinal adverse effects (nausea, vomiting, diarrhea)","Increased heart rate","Suicidal behavior and ideation (monitor)"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

SEMAGLUTIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEMAGLUTIDE (SEMAGLUTIDE).

How it works

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases insulin secretion, decreases glucagon secretion, slows gastric emptying, and reduces appetite and food intake.

What the body does with it

Metabolism	Semaglutide is metabolized via proteolytic cleavage of the peptide backbone and sequential beta-elimination of the C-terminal dipeptide. It is not primarily metabolized by CYP enzymes.
Excretion	Renal: 0%; Biliary/Fecal: ~97% as parent and metabolites; Urine: <3% as metabolites
Half-life	Terminal elimination half-life: ~1 week (168 hours) due to extensive plasma protein binding and reduced renal clearance, supporting once-weekly dosing
Protein binding	>99% bound to albumin
Volume of Distribution	Approximately 12.5 L (0.16 L/kg for a 75 kg patient), indicating limited extravascular distribution
Bioavailability	Subcutaneous: ~89%
Onset of Action	Subcutaneous: Glycemic effects begin within 2-4 weeks; significant HbA1c reduction observed by 8-12 weeks
Duration of Action	Subcutaneous: Weekly dosing maintains therapeutic concentrations for 7 days; clinical effects persist for up to 14 days after last dose due to long half-life

Classification & Brands

Dosing & administration

Subcutaneous injection once weekly, starting at 0.25 mg for 4 weeks, then 0.5 mg for 4 weeks, then may increase to 1 mg, 1.7 mg, or 2.4 mg based on glycemic response and tolerability.

Dosage form	INJECTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR >=30 mL/min/1.73 m2). Limited data in severe renal impairment (eGFR <30 mL/min/1.73 m2); use with caution due to increased exposure and gastrointestinal adverse effects. Not recommended in end-stage renal disease.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution.
Pediatric use	Not approved for patients <18 years of age. Safety and efficacy not established.
Geriatric use	No dose adjustment required based on age alone. Monitor renal function and tolerability, as elderly patients may be more sensitive to gastrointestinal effects and 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 SEMAGLUTIDE (SEMAGLUTIDE).

Breastfeeding	No human data; drug is excreted in rat milk. M/P ratio unknown. Theoretical risk of adverse effects in infant due to GLP-1 receptor agonism. Because of high molecular weight, significant transfer is unlikely, but caution advised.
Teratogenic Risk	First trimester: Limited human data; animal studies show embryotoxicity and malformations at high doses. Second and third trimesters: No adequate human studies; potential fetal harm due to maternal weight loss and nutritional deficiencies. GLP-1 receptor agonists may cause fetal growth restriction.

Warnings & precautions

■ FDA Black Box Warning

There is no FDA-issued boxed warning for semaglutide.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Personal or family history of medullary thyroid carcinoma","Multiple endocrine neoplasia syndrome type 2","Hypersensitivity to semaglutide or any components","Pregnancy (due to weight loss risks)"]