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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

  1. For pre-filled pens, attach a new needle and prime per instructions.
  2. For vials, draw prescribed dose with appropriate syringe.
  3. Clean injection site with alcohol and allow to dry.
  4. Inject subcutaneously at 90° (or 45° if lean).
  5. Hold for ~6 seconds after injection to ensure full dose delivery.
  6. 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.