Semaglutide
Ozempic · Wegovy · Rybelsus · GLP-1 RA
−14.9% mean body weight at 68 weeks (STEP 1)
Overview
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist engineered for once-weekly dosing. Structural modifications to the native GLP-1 backbone — an amino-acid substitution that resists DPP-4 degradation plus a fatty-acid chain that binds albumin — extend its half-life to roughly seven days, allowing steady receptor engagement from a single weekly injection.
In clinical use it lowers blood glucose in a glucose-dependent manner and substantially reduces appetite and energy intake. The pivotal STEP program in people with overweight or obesity (without diabetes) reported a mean body-weight reduction of about 14.9% over 68 weeks at the 2.4 mg dose, versus roughly 2.4% on placebo.
Because gastrointestinal tolerability is the main limiter, semaglutide is titrated slowly over months. The figures and schedules summarized here reflect the published label and trial protocols and are provided strictly as a research reference.
Key parameters
- Dose range
- 0.25–2.4 mg weekly
- Frequency
- Once weekly
- Half-life
- ~7 days (≈165 h)
- Route
- Subcutaneous
- Vial sizes
- 2 mg · 5 mg · 10 mg
- Regulatory status
- FDA-approved as Ozempic (2017, type 2 diabetes) and Wegovy (2021, chronic weight management). Research-vial material is not an approved drug product and is labeled for laboratory use only.
Mechanism of action
GLP-1 receptor agonism (CNS appetite centers)
Activates GLP-1 receptors in the hypothalamus and hindbrain, increasing satiety and reducing hunger and food reward, which lowers overall energy intake.
Glucose-dependent insulin secretion
Stimulates pancreatic beta-cells to release insulin only when glucose is elevated, improving glycemic control with a low intrinsic hypoglycemia risk.
Glucagon suppression
Reduces inappropriate glucagon secretion from pancreatic alpha-cells, decreasing hepatic glucose output.
Delayed gastric emptying
Slows the rate at which the stomach empties, prolonging fullness after meals — also the basis of early nausea during titration.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Initiation | Weeks 1–4 | 0.25 mg once weekly | Non-therapeutic starting dose intended only to reduce GI side effects. |
| Titration step 1 | Weeks 5–8 | 0.5 mg once weekly | — |
| Titration step 2 | Weeks 9–12 | 1.0 mg once weekly | — |
| Titration step 3 | Weeks 13–16 | 1.7 mg once weekly | — |
| Maintenance | Week 17 onward | 2.4 mg once weekly | Target maintenance dose in the STEP obesity trials; some protocols hold at a lower tolerated dose. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
5 mg vial + 2 mL bacteriostatic water
Concentration2,500 mcg/mL · 2.5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 250 mcg | 0.1 mL | 10 |
| 500 mcg | 0.2 mL | 20 |
| 1,000 mcg | 0.4 mL | 40 |
| 1,700 mcg | 0.68 mL | 68 |
Convenient mix for the early titration range (0.25–1.0 mg).
10 mg vial + 2 mL bacteriostatic water
Concentration5,000 mcg/mL · 5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 500 mcg | 0.1 mL | 10 |
| 1,000 mcg | 0.2 mL | 20 |
| 1,700 mcg | 0.34 mL | 34 |
| 2,400 mcg | 0.48 mL | 48 |
Higher-strength mix that keeps the 2.4 mg maintenance draw inside a 50-unit syringe.
Reconstitution calculator
Pre-filled with Semaglutide's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 1,000 micrograms per millilitre, a 250 microgram dose is 0.25 millilitres, or 25 units on a U-100 syringe, giving 8 doses per vial.
Supplies needed
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Recommended supply
Semaglutide — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
Per the Wegovy label: if a dose is missed and the next scheduled dose is more than 48 hours away, administer as soon as possible; if it is within 48 hours, skip the missed dose and resume the normal weekly schedule. If more than two consecutive weekly doses are missed, re-initiation at a lower dose with re-titration may be considered.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Gastrointestinal | NauseaSTEP 1; mostly mild–moderate and concentrated during titration. | 44% |
| Gastrointestinal | Diarrhea | 32% |
| Gastrointestinal | Vomiting | 25% |
| Gastrointestinal | Constipation | 24% |
| Hepatobiliary | Gallstones / cholelithiasisMore common with rapid or large weight loss. | 3% |
| General | Fatigue / headache | — |
Clinical trials & evidence
STEP 1
Phase 368 weeks · 1,961 adults with overweight/obesity, without diabetes
−14.9% body weight vs −2.4% placebo; ~86% lost ≥5%.
NCT03548935 ↗STEP 4 (maintenance)
Phase 368 weeks · Adults who completed a 20-week run-in
Continued semaglutide lost a further ~7.9%; switching to placebo regained ~6.9%.
NCT03548987 ↗SELECT (cardiovascular outcomes)
Phase 3~40 months (mean) · 17,604 adults with CVD and overweight/obesity, without diabetes
20% relative reduction in major adverse cardiovascular events.
NCT03574597 ↗
Storage & handling
- Lyophilized
- Lyophilized powder is stable refrigerated at 2–8 °C; short excursions to room temperature are tolerated. Protect from light.
- Reconstituted
- After reconstitution, refrigerate at 2–8 °C and use within ~28–56 days. Do not freeze.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| Tirzepatide | GLP-1 only vs GIP + GLP-1 | ~7 d vs ~5 d | 0.25–2.4 mg weekly vs 2.5–15 mg weekly | −14.9% vs up to −20.9% (different trials) | Both FDA-approved for obesity |
| Liraglutide | GLP-1 (both) | ~7 d vs ~13 h | Weekly vs daily | Greater weight loss with semaglutide head-to-head | Both FDA-approved |
| Retatrutide | GLP-1 vs GIP + GLP-1 + glucagon | ~7 d vs ~6 d | Weekly (both) | −14.9% vs −24.2% (different trials/phases) | Approved vs investigational |
Featured in these stacks
CagriSema (Cagrilintide + Semaglutide)
CagriSema combines a long-acting amylin analog (cagrilintide) with a GLP-1 agonist (semaglutide), each titrated toward 2.4 mg weekly. The two appetite mechanisms — amylin-mediated and GLP-1-mediated satiety — are additive, and the combination has advanced through Phase 3 (REDEFINE) as a fixed-dose product.
Sources & references
- [1]Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med 2021. ↗ source
- [2]Lincoff AM et al. Semaglutide and Cardiovascular Outcomes (SELECT). N Engl J Med 2023. ↗ source
- [3]FDA Prescribing Information — Wegovy (semaglutide) injection. ↗ source
- [4]ClinicalTrials.gov — STEP 1 (NCT03548935). ↗ source
Frequently asked questions
Why is semaglutide titrated so slowly?
Gastrointestinal side effects — nausea in particular — are dose- and speed-dependent. The four-week step-ups give the gut time to adapt, which is why the label starts at a sub-therapeutic 0.25 mg.
What is the difference between Ozempic and Wegovy?
Both are semaglutide. Ozempic is approved for type 2 diabetes (up to 2.0 mg), while Wegovy is approved for weight management at a higher 2.4 mg target dose.
Does weight return after stopping?
STEP 4 showed substantial weight regain after discontinuation, consistent with GLP-1 agonists modifying appetite rather than permanently resetting it.
Related protocols
Tirzepatide
Mounjaro
−20.9% body weight at 72 weeks, 15 mg (SURMOUNT-1)
Retatrutide
LY3437943
−24.2% body weight at 48 weeks, 12 mg (Phase 2, NEJM 2023)
Cagrilintide
AM833
−10.8% body weight at 26 weeks (monotherapy, Lancet 2021)
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For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.