Semaglutide
/ Long-acting GLP-1 receptor agonistALIAS · Ozempic · Wegovy · Rybelsus
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FDA-approved for type 2 diabetes (2017), chronic weight management (2021), cardiovascular risk reduction in obesity (2024), and diabetic kidney disease (2025).
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist — a modified human GLP-1 analog with an Aib substitution at position 8 (resisting DPP-4 cleavage) and a C18 fatty-diacid side chain at Lys26 that drives albumin binding and extends plasma half-life to approximately 165 hours.
Activation of pancreatic beta-cell GLP-1 receptors enhances glucose-dependent insulin secretion and suppresses glucagon. Hypothalamic and brainstem GLP-1 receptors slow gastric emptying and increase satiety. Unlike tirzepatide, semaglutide is a pure GLP-1R mono-agonist with no meaningful GIP activity.
Extensive. Multiple large phase-3 randomized controlled trials support approvals for type 2 diabetes (SUSTAIN program), chronic weight management (STEP program), cardiovascular risk reduction in obesity without diabetes (SELECT), and diabetic kidney disease (FLOW).
Factual reporting of what cited studies used — not a recommendation.
- STEP 1 obesity phase-3 trial — Adult humans without diabetes — Titrated to 2.4 mg Subcutaneous weeklyREFSTEP 1 (Wilding 2021)
- SUSTAIN-6 T2DM cardiovascular outcomes trial — Adult humans with type 2 diabetes and established CV risk — 0.5 or 1.0 mg Subcutaneous weeklyREFSUSTAIN-6 (Marso 2016)
In pivotal trials the most common adverse events were gastrointestinal (nausea up to ~44% in STEP 1, diarrhea, vomiting, constipation) — generally mild to moderate and titration-related. Boxed warning for thyroid C-cell tumors based on rodent findings; human relevance is not established. Warnings in labeling include pancreatitis, gallbladder disease, acute kidney injury from dehydration, diabetic retinopathy complications (SUSTAIN-6 HR 1.76), and hypoglycemia when combined with insulin or sulfonylureas.
Regulatory status
- FDA status:
- FDA-approved
- Compounding:
- Not eligible for compounding (approved, not in shortage)
The FDA removed semaglutide from its drug shortage list in October 2024. As of 2026, compounding essentially-a-copy semaglutide is not permitted by 503A or 503B facilities absent a documented clinical difference for an individual patient. Salt forms such as semaglutide sodium were explicitly ruled out as valid APIs for compounding. FDA has issued multiple warning letters to online sellers marketing unapproved GLP-1 products.