Semaglutide

Summary

Semaglutide is a long-acting GLP-1 receptor agonist approved for the treatment of type 2 diabetes mellitus and chronic weight management. It is available in subcutaneous injectable form (Ozempic for T2DM; Wegovy for obesity) and as an oral tablet (Rybelsus for T2DM). It has demonstrated significant HbA1c reduction, body weight reduction, and cardiovascular risk reduction in clinical trials.

Mechanism of Action

Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that binds and activates the GLP-1 receptor, stimulating glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite via central hypothalamic pathways.

Routes of Administration

Goals & Uses

• Non-alcoholic steatohepatitis (NASH)HepaticModerate
• Cardiovascular risk reductionCardiovascularHigh
• Chronic weight management / obesityWeight ManagementHigh
• Glycemic control in type 2 diabetesMetabolicHigh
• Kidney disease risk reduction in T2DMRenalModerate
• Appetite suppression / satietyMetabolicHigh

Contraindications

• Diabetic ketoacidosisMetabolicHigh
• Personal or family history of medullary thyroid carcinoma (MTC)OncologicHigh
• Multiple endocrine neoplasia syndrome type 2 (MEN2)OncologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• History of serious hypersensitivity to semaglutideImmunologicHigh

Adverse Effects

• Injection site reactionsLocalUncommon
• Diabetic retinopathy complicationsOphthalmologicUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• VomitingGastrointestinalCommonForceful expulsion of stomach contents
• Acute pancreatitisGastrointestinalRare
• DiarrheaGastrointestinalCommonLoose or frequent stools

Drug Interactions

• Oral medications (general)Low
• WarfarinModerate
• Insulin / Insulin secretagogues (sulfonylureas)High

Population Constraints

• Pediatric patients (<18 years)AgeRelative
• Severe renal impairment / End-stage renal diseaseRenalRelative
• History of pancreatitisGastrointestinalRelative
• Severe hepatic impairmentOrgan ImpairmentRelative
• Pregnancy and lactationReproductiveAbsolute

Regulatory Status

• European UnionApprovedApproved: Type 2 diabetes mellitus (Ozempic SC; Rybelsus oral), Weight management in adults with obesity or overweight with weight-related comorbidities (Wegovy SC)EMA approved Ozempic February 2018; Rybelsus April 2020; Wegovy January 2022.
• United StatesApprovedApproved: Type 2 diabetes mellitus (Ozempic SC; Rybelsus oral), Chronic weight management in adults with obesity or overweight with comorbidity (Wegovy SC), Cardiovascular risk reduction in adults with established CVD and obesity/overweight (Wegovy SC, 2024), Reduction of risk of worsening kidney disease in adults with T2DM and CKD (2024)FDA first approved Ozempic December 2017; Rybelsus September 2019; Wegovy June 2021. REMS not required but thyroid cancer risk warning in labeling.
• United KingdomApprovedApproved: Type 2 diabetes mellitus (Ozempic SC; Rybelsus oral), Chronic weight management (Wegovy SC)MHRA approvals align broadly with EMA decisions post-Brexit. Wegovy approved 2023 in UK; subject to NHS access negotiations.

FDA-approved for T2DM (Ozempic, 2017; Rybelsus, 2019) and chronic weight management (Wegovy, 2021). EMA and MHRA approvals also granted. Wegovy received additional cardiovascular risk reduction indication in the US in 2024 (SELECT trial). Black Box Warning: risk of thyroid C-cell tumors observed in rodents; contraindicated in patients with personal/family history of medullary thyroid carcinoma or MEN2.

Evidence & Sources

No sources recorded yet.