The GLP-1 receptor agonist behind Ozempic and Wegovy — how it works, how to titrate safely, and what to expect from weekly dosing.
Semaglutide is a GLP-1 receptor agonist — a synthetic analog of glucagon-like peptide-1 (GLP-1), a hormone your gut releases after eating. Natural GLP-1 breaks down within minutes; semaglutide is modified to last around a week, allowing once-weekly dosing.
It is FDA approved as Ozempic (for type 2 diabetes) and Wegovy (for weight management) — the same molecule at different dose ceilings. Phase 3 trials (STEP and SUSTAIN) showed an average 15% body-weight reduction at the 2.4 mg dose.
FDA approved. Prescription-only in the US. Available from compounding pharmacies and (outside the US supply chain) research suppliers. Not WADA prohibited.
Acts on GLP-1 receptors in the hypothalamus to reduce hunger and increase the feeling of fullness. Most users report significantly reduced “food noise.”
Slows how fast food leaves the stomach, extending fullness per meal. This is also why nausea is the most common early side effect.
Enhances glucose-dependent insulin secretion and suppresses glucagon — lowers HbA1c without causing hypoglycemia in non-diabetics.
SELECT trial (2023) showed a 20% reduction in major cardiovascular events in overweight/obese patients with existing cardiovascular disease — independent of diabetes status.
Semaglutide is one of the most rigorously studied weight-management drugs ever approved — with decades of GLP-1 biology and multiple Phase 3 programs.
| Benefit | Evidence |
|---|---|
| Weight loss | STEP 1 trial: ~15% body-weight loss at 68 weeks on 2.4 mg weekly |
| HbA1c reduction | SUSTAIN program: HbA1c drops of 1.5–1.8% in type 2 diabetes |
| Cardiovascular events | SELECT: 20% reduction in MACE (heart attack, stroke, CV death) in non-diabetic obese |
| Kidney protection | FLOW trial (2024): 24% reduction in kidney disease progression |
| Addiction / craving | Emerging evidence of reduced alcohol and nicotine cravings via mesolimbic dopamine pathway |
| Liver health | Improvements in NAFLD / MASH markers |
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeSlow titration is critical. Jumping doses is the #1 cause of severe GI side effects.
| Weeks | Weekly Dose |
|---|---|
| 1–4 | 0.25 mg |
| 5–8 | 0.50 mg |
| 9–12 | 1.0 mg |
| 13–16 | 1.7 mg |
| 17+ | 2.4 mg (max) |
If side effects at any step, hold for an extra 4 weeks before advancing. Some users find the “sweet spot” at 1.0–1.7 mg and never need the max dose.
Once at goal weight, many users drop back to a maintenance dose (0.5–1.0 mg weekly) to keep appetite suppression without max side effects. Full discontinuation frequently leads to substantial weight regain — STEP 4 (PMID 33755728) showed participants who switched to placebo after a 20-week run-in regained ~7 percentage points of body weight over the following 48 weeks, while those continuing semaglutide lost an additional ~8%. Plan for long-term dosing rather than a short course.
Semaglutide from research suppliers typically comes as a 5 mg or 10 mg lyophilized vial. Branded Ozempic/Wegovy pens come pre-filled and do not need reconstitution.
5 mg vial + 2 mL BAC water = 2.5 mg/mL = 2500 mcg/mL
| Dose | Volume | Syringe Units |
|---|---|---|
| 0.25 mg | 0.10 mL | 10 units |
| 0.50 mg | 0.20 mL | 20 units |
| 1.0 mg | 0.40 mL | 40 units |
| 1.7 mg | 0.68 mL | 68 units |
| 2.4 mg | 0.96 mL | 96 units |
5 mg vial at 0.5 mg/week = 10 weeks; at 2.4 mg/week = ~2 weeks
Use our free peptide calculator to figure out your reconstitution volume, draw amount, and syringe units.
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FDA boxed warning for thyroid C-cell tumors (based on rodent data; human relevance uncertain but strictly avoid with MTC/MEN2 history).
How much protein do I need while on semaglutide?
Target at least 1 g protein per pound of lean body mass and strength train 2–3×/week to preserve muscle during weight loss.
What if nausea is severe?
Eat smaller meals, avoid high-fat meals, stay hydrated. If persistent or severe vomiting occurs, hold the dose and work with a doctor — this is not normal.
Do I need labs?
Baseline CBC, CMP (including liver and kidney), lipase/amylase, thyroid panel, HbA1c. Recheck every 3–6 months. Monitor heart rate (can increase with GLP-1s).
Semaglutide vs. tirzepatide?
Tirzepatide (Mounjaro / Zepbound) is a dual GLP-1/GIP agonist — more weight loss on average. The 2025 SURMOUNT-5 head-to-head (PMID 40353578) showed ~20% weight loss on tirzepatide vs. ~14% on semaglutide at 72 weeks in obesity without T2D. Side-effect profiles are broadly similar; semaglutide has more long-term safety data.
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Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
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