Semaglutide
Also known as: Ozempic, Wegovy, Rybelsus
Overview
Semaglutide is an FDA-approved synthetic 31-amino acid analog of glucagon-like peptide-1 (GLP-1), modified with a C18 fatty acid chain via a linker to albumin for extended half-life (~7 days). Originally approved for type 2 diabetes (Ozempic, 2017), it received approval for chronic weight management (Wegovy, 2021) after demonstrating ~15% average body weight reduction in the STEP-1 trial. It has since demonstrated remarkable cardiovascular benefits (20% reduction in MACE in the SELECT trial) and is being investigated for kidney disease, NASH, Alzheimer's disease, and addiction.
Mechanism of Action
Semaglutide activates GLP-1 receptors (GLP-1R) expressed in the pancreas, brain (hypothalamus, brainstem), heart, kidney, and other tissues. In the pancreas, glucose-dependent insulin secretion is increased while glucagon suppression reduces hyperglycemia. In the hypothalamus and brainstem, GLP-1R activation reduces appetite and food intake by modulating arcuate nucleus satiety neurons and reducing reward-circuit food cue responses. Peripheral effects include slowed gastric emptying (enhancing satiety), improved insulin sensitivity, reduced liver fat, and direct cardiovascular protection.
Potential Benefits
- FDA-approved: type 2 diabetes (Ozempic), obesity (Wegovy), cardiovascular risk reduction
- ~15% average body weight reduction in STEP-1 trial
- 20% reduction in major adverse cardiovascular events in SELECT trial
- 1.5% HbA1c reduction in type 2 diabetes
- Reduced all-cause mortality in cardiovascular risk patients
- Kidney disease progression reduction (Phase III data)
- Emerging evidence for Alzheimer's disease, NASH, and alcohol use disorder
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Typical Range | 0.25-2.4 mg/week (subcutaneous); 3-14 mg/day (oral) |
| Beginner | 0.25 mg/week for 4 weeks (titration start) |
| Intermediate | 0.5-1 mg/week |
| Advanced | 1.7-2.4 mg/week (FDA-approved obesity dose) |
| Cycle Duration | Ongoing; no defined off-cycle for therapeutic use |
| Cycle Off | Discontinuation results in weight regain; not intended for cycling |
FDA-approved titration: 0.25 mg/week → 0.5 mg (wk 5) → 1 mg (wk 9) → 1.7 mg (wk 13) → 2.4 mg (wk 17). Oral semaglutide taken on empty stomach with ≤4 oz water.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection High — systemic distribution
Most common administration route for research peptides. Inject into abdominal fat, thigh, or upper arm. Rotate sites. standard research dose.
Intramuscular Injection High — with slightly faster onset than SC
Alternative route when deeper delivery or faster absorption is desired. Less commonly used than SC for most research peptides.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving Semaglutide:
Metabolic Health Stack
Combines Semaglutide with MOTS-c (mitochondrial metabolism) and AOD-9604 (lipolysis) for metabolic optimization.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Typical Vial Size | 2mg/1.5ml, 4mg/3ml pen device, Oral 3mg, 7mg, 14mg tablets |
|---|---|
| BAC Water | N/A — supplied as pre-mixed solution in auto-injector pens |
| Storage | Refrigerate unused pens at 2-8°C; in-use pens may be stored at room temperature up to 30°C for 56 days |
| Shelf Life | 18-24 months unopened; 56 days after first use |
Need exact syringe measurements?
Amino Acid Sequence
His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(C18-fatty acid-linker)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg
Side Effects & Safety
- Nausea (most common, dose-dependent)
- Vomiting and diarrhea
- Constipation
- Decreased appetite
- Risk of pancreatitis (rare)
- Thyroid C-cell tumor risk in animal models (clinical significance uncertain)
- Gallbladder disease
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Personal or Family History of Medullary Thyroid Carcinoma or MEN 2
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
Drug Interactions
- Oral Medications (general):
FDA Safety Information
FDA Boxed Warning: Risk of thyroid C-cell tumors. Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Pharmacokinetics
| Half-Life | ~165 hours (~1 week) |
|---|---|
| Storage | Pens: refrigerate at 2-8°C before first use. After first use, store at room temperature (up to 30°C) for up to 56 days or refrigerated. Do not freeze. |
Synergistic Compounds
The following compounds have been studied alongside Semaglutide for potential complementary or synergistic effects:
Learn More
References & Further Reading
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