Semaglutide¶
Tags: Weight Loss, Diabetes, GLP-1
Quick Summary
Semaglutide is a long‑acting GLP‑1 receptor agonist with robust evidence for weight loss and glycemic control; once-weekly dosing improves adherence.
Quick Facts¶
- Typical Dose: 0.25–2.4 mg weekly (titrated)
- Route: Subcutaneous injectable (abdomen, thigh, upper arm)
- Cycle: Ongoing as prescribed (titrate to target dose)
- Storage: Refrigerate 2–8°C before use; some products stable at room temp for limited periods
Overview¶
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist FDA-approved for type 2 diabetes (Ozempic) and chronic weight management (Wegovy). Extensive clinical trials demonstrate significant weight loss and improved glycemic control via appetite suppression, slowed gastric emptying, and enhanced glucose-dependent insulin secretion.
Key Benefits¶
- Clinically proven weight loss (average 15–20% in trials at 2.4 mg)
- Improved glycemic control for type 2 diabetes
- Once-weekly dosing for convenience
- Cardiovascular outcome benefits in high-risk populations
Mechanism of Action¶
Semaglutide binds GLP-1 receptors, augmenting glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite via central pathways. A long half-life (approx. 7 days) enables weekly dosing.
Molecular Information¶
- Weight: 4,113.64 Da
- Length: 31 amino acids
- Type: GLP-1 receptor agonist
Amino Acid Sequence:
His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly
Acylated with C18 fatty diacid via γ-Glu spacer for extended half-life.
Research Protocols¶
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Weight Loss Initiation | 0.25 mg | Weekly x 4 weeks, then increase | Subcutaneous |
| Weight Loss Maintenance | 2.4 mg | Weekly (after 16-week titration) | Subcutaneous |
| Diabetes Management | 0.5–1 mg | Weekly | Subcutaneous |
| Cardiovascular Protection | 0.5–1 mg | Weekly | Subcutaneous |
| Tolerability-Based | 0.25–2.4 mg | Weekly (individualized) | Subcutaneous |
Timing: Inject on the same day each week. If a dose is missed and within 5 days, take it; otherwise skip and resume the regular schedule.
How to Reconstitute / Inject¶
- For pre-filled pens, attach a new needle and prime per instructions.
- For vials, draw prescribed dose with appropriate syringe.
- Clean injection site with alcohol and allow to dry.
- Inject subcutaneously at 90° (or 45° if lean).
- Hold for ~6 seconds after injection to ensure full dose delivery.
- Dispose of needles safely and rotate injection sites weekly.
Peptide Interactions¶
Avoid
- Tirzepatide — avoid combination due to overlapping incretin effects and hypoglycemia risk.
Monitor
- Insulin — monitor and adjust doses to avoid hypoglycemia.
- Sulfonylureas — monitor for hypoglycemia when combined.
- Oral medications — timing may be required due to slowed gastric emptying.
Compatible / Synergistic
- Cagrilintide — synergistic in combination protocols (clinical monitoring advised).
- Metformin — compatible and commonly co‑prescribed.
- Growth Hormone Peptides / BPC‑157 — generally compatible.
Quality Indicators¶
Positive Signs
- FDA‑approved branded products (Ozempic, Wegovy) from licensed pharmacies
- Proper storage verification and clear solution after reconstitution
- Stable packaging and visible batch/lot information
Warning Signs
- Cloudy, discolored, or particulate solutions — do not use
- Compounded/non‑pharmacy sources without COA — avoid when possible
- Improper storage temperatures or damaged seals
What to Expect¶
- Week 1–4: Mild appetite reduction, possible nausea during titration
- Month 2–3: Noticeable weight loss (5–10% typical), improved satiety
- Month 4–6: Continued weight loss (10–15% common), stable glucose
- Month 6+: Possible plateau; maintenance with continued therapy
- Diabetes benefits may appear within 1–2 weeks
Side Effects & Safety¶
- Common: nausea, diarrhea, vomiting, constipation
- Start low and titrate to minimize GI side effects
- Contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2
- Monitor for pancreatitis (severe abdominal pain)
- Not recommended in pregnancy or breastfeeding
References¶
STEP 1 Trial - Weight Management (2021)
Human | 1,961 participants | 2.4 mg weekly | 68 weeks Key result: ~14.9% mean weight loss at 68 weeks.
SELECT Cardiovascular Outcomes (2023)
Human | 17,604 participants | 2.4 mg weekly | Long-term outcomes Key result: cardiovascular risk reduction observed in high‑risk populations.
SUSTAIN Diabetes Program (2016–2019)
Multiple clinical trials | 0.5–1 mg weekly Demonstrated consistent HbA1c reductions across patient populations.