Semaglutide: Complete Guide
Semaglutide is an FDA-approved GLP-1 receptor agonist used for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy). It mimics the incretin hormone GLP-1, stimulating insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite through central nervous system signaling. Clinical trials demonstrated unprecedented weight loss results, with participants losing 15–17% of body weight on average.
Last updated: 2026-01-29
Quick Facts
- Category
- glp1
- Also Known As
- Ozempic, Wegovy, Rybelsus
- Related Goals
- weight loss
Who Researches Semaglutide?
Semaglutide is the most widely prescribed GLP-1 agonist for weight management and type 2 diabetes. It's relevant for researchers comparing incretin-based therapies, those studying metabolic health, and anyone investigating the GLP-1 class that includes tirzepatide, retatrutide, and liraglutide. As an FDA-approved medication with robust Phase 3 data, semaglutide has the strongest evidence base in the GLP-1 peptide category.
Related Resources
Research Peptides
We may earn a commission if you purchase through this link, at no extra cost to you.
What Is Semaglutide?
Semaglutide is a synthetic GLP-1 (glucagon-like peptide-1) analog with 94% structural homology to native human GLP-1. Developed by Novo Nordisk, it incorporates key modifications — an acyl chain attached via a linker to position 26 — that enable binding to albumin, extending its half-life to approximately 7 days (versus 2 minutes for native GLP-1). This allows once-weekly dosing.
Three formulations are FDA-approved: Ozempic (injectable, type 2 diabetes), Wegovy (injectable, chronic weight management), and Rybelsus (oral tablet, type 2 diabetes). The STEP clinical trial program demonstrated that 2.4 mg weekly semaglutide produced mean weight loss of 14.9% over 68 weeks — results that fundamentally changed the obesity treatment landscape.
Mechanism of Action
Semaglutide activates GLP-1 receptors throughout the body, producing multiple metabolic effects:
- Pancreatic effects: Stimulates glucose-dependent insulin secretion and suppresses inappropriate glucagon release from alpha cells
- Central appetite suppression: Activates GLP-1 receptors in the hypothalamus and brainstem, reducing hunger and increasing satiety
- Gastric emptying: Slows the rate at which food leaves the stomach, contributing to fullness and reduced caloric intake
- Cardiovascular effects: The SUSTAIN-6 and SELECT trials demonstrated cardiovascular risk reduction independent of glucose control
Researching peptides? We did the hard part.
Get our free Peptide Starter Kit — the 5 most researched compounds, simplified into one actionable guide.
Dosage Overview
| Indication | Brand | Starting Dose | Target Dose | Route |
|---|---|---|---|---|
| Type 2 Diabetes | Ozempic | 0.25 mg/week | 0.5–1 mg/week | SC injection |
| Weight Management | Wegovy | 0.25 mg/week | 2.4 mg/week | SC injection |
| Type 2 Diabetes | Rybelsus | 3 mg/day | 7–14 mg/day | Oral tablet |
Dose escalation follows a gradual schedule over 16–20 weeks to minimize gastrointestinal side effects. The injection is administered once weekly on the same day each week, in the abdomen, thigh, or upper arm.
Side Effects & Safety
- Nausea (20–44%): Most common side effect, typically improves with dose escalation
- Vomiting (5–24%)
- Diarrhea (8–30%)
- Constipation (5–24%)
- Injection site reactions: Mild and transient
- Pancreatitis: Rare but reported — discontinue if suspected
- Thyroid C-cell tumors: Boxed warning based on rodent studies; contraindicated with personal/family history of MTC or MEN2
- Gallbladder events: Increased incidence of cholelithiasis
Related GLP-1 Compounds
Semaglutide is one of several GLP-1-based therapies, each with distinct receptor profiles and clinical data. For a comprehensive overview, see the complete GLP-1 guide.
- Tirzepatide (Mounjaro/Zepbound): A dual GLP-1/GIP agonist that produced up to 22.5% weight loss in the SURMOUNT-1 trial — superior to semaglutide in head-to-head comparison (Jastreboff et al., NEJM 2022). Consider tirzepatide if semaglutide has not produced sufficient results.
- Retatrutide: A triple GLP-1/GIP/glucagon agonist in Phase 3 trials showing up to 24.2% weight loss. The added glucagon agonism increases energy expenditure and dramatically reduces liver fat.
- Liraglutide (Victoza/Saxenda): The first-generation GLP-1 agonist with daily dosing. Produces ~8% weight loss — less than semaglutide but with longer real-world safety data.
- Cagrilintide (CagriSema): An amylin analog studied in combination with semaglutide. The CagriSema combination demonstrated 22.7% weight loss in Phase 3 by targeting both amylin and GLP-1 pathways.
- Survodutide: A dual GLP-1/glucagon agonist showing 18.7% weight loss and strong MASH improvement data.
- Mazdutide: Another dual GLP-1/glucagon agonist in Phase 3 trials, primarily studied in China.