Overview
Semaglutide (Ozempic / Wegovy) is an FDA-approved long-acting synthetic glucagon-like peptide-1 (GLP-1) receptor agonist engineered for weekly administration.
What problem it targets: It targets obesity, chronic overeating, intense food cravings ("food noise"), Type 2 diabetes, and high cardiovascular disease risk in overweight adults.
What It Does
• Shuts down central appetite signaling: Binds GLP-1 receptors in the brain's hypothalamus, eliminating chronic hunger signals and making caloric restriction feel effortless.
• Prolongs stomach fullness: Slows gastric emptying rate, keeping food in the digestive tract longer and flattening post-meal blood sugar surges.
• Optimizes insulin and glucagon balance: Triggers glucose-dependent insulin release while halting inappropriate liver glucose dumps into the bloodstream.
• Realistic expectations: Injected once weekly. Titrated slowly over 16 to 20 weeks (0.25 mg up to 2.4 mg) to manage initial nausea, resulting in dependable, long-term fat reduction of 15% or more.
Reconstitution
| Vial size | BAC water | Concentration |
|---|---|---|
| 10 mg | + 2 mL | 5 mg/mL |
| 15 mg | + 3 mL | 5 mg/mL |
| 20 mg | + 4 mL | 5 mg/mL |
| 50 mg | + 10 mL | 5 mg/mL |
Protocol
| Weeks | Dose | Notes |
|---|---|---|
| Weeks 1–4 | 0.25 mg/wk | FDA Wegovy starting dose. At U-100 precision floor; draw carefully. Hold 4 wks, most GI side effects occur early. |
| Weeks 5–8 | 0.5 mg/wk | FDA step 2. Step up only if Weeks 1–4 tolerated. (Ozempic maintenance range.) |
| Weeks 9–12 | 1 mg/wk | FDA step 3. Ozempic max is 2 mg/wk; higher steps are Wegovy-only. |
| Weeks 13–16 | 1.7 mg/wk | FDA step 4 (Wegovy intermediate). |
| Weeks 17+ | 2.4 mg/wk | FDA Wegovy maintenance (maximum). Stop at any earlier rung that controls appetite without intolerable side effects. Cycle: Ongoing per FDA Wegovy/Ozempic labels; no scheduled off-cycle. Discontinue ≥2 months before planned pregnancy (long half-life). Timing: Weekly, same day each week. FDA indications (injectable): T2D glycemic control; CV-risk reduction (established CVD); CKD (FLOW, Jan 2025); MASH with F2–F3 fibrosis (Wegovy, Aug 2025). 2026 compounding: FDA proposed removing semaglutide / tirzepatide / liraglutide from the 503B bulks list (public comments to Jun 29, 2026); 503A compounding continues under added scrutiny. Women: Women lose more than men at the same dose but report more GI (start lower). In PCOS they improve cycles, lower free testosterone and raise ovulation; a real unplanned-pregnancy risk. Stop before conceiving. Men: In men, excess fat lowers testosterone; GLP-1 raises total testosterone, SHBG and gonadotropins as weight drops, and improves sperm and erectile function; and preserves fertility, unlike TRT (which suppresses sperm). |
Handling & Stacking
Injection site
Abdomen, outer thigh, or upper arm.
Storage
- Freeze-dried: -4°F.
- Reconstituted: 36–46°F.
- Best used within 28 days.
- No clear reconstituted-potency data (the pen label gives an in-use date, not potency), so defer to the 28-day sterility limit; commercial pens follow their own pen date.
Side effects
Nausea, vomiting, diarrhea, constipation, decreased appetite. Rare: NAION (sudden, usually irreversible vision loss); added to EU labels 2025; pooled risk ~2× vs non-users.
What to expect
- Appetite reduction within week 1.
- Nausea peaks weeks 1–4 then diminishes.
- Weight loss most apparent at 12–16 weeks.
- Titrate slowly to minimise GI side effects.
- Supply math 10mg → 5 vials | 15mg → 3 | 20mg → 3 | 50mg → 1 vial (17-wk @ 2.4 mg × 1/wk)
Pairs well with
MOTS-c (mitochondrial energy during caloric deficit); Lipo-C (lipotropic adjunct); Vitamin B12 (counters GLP-1 B12 depletion)
Avoid
Tirzepatide or Retatrutide simultaneously, or any other GLP-1 receptor agonist (receptor desensitisation + additive GI nausea, hypoglycaemia)
FDA Label vs Community Dosing
| Approach | Ramp / dose (weekly) | Philosophy |
|---|---|---|
| FDA, Wegovy (weight loss) | 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg, +4 wks per step | Escalate to the max approved dose (2.4 mg) for maximum weight loss. |
| FDA, Ozempic (type-2 diabetes) | 0.25 → 0.5 → 1.0 → up to 2.0 mg | Glycemic control; lower ceiling than Wegovy. |
| Community | Same ramp, but hold at the lowest effective dose (often | Titrate to effect, not to the max; step up only if progress stalls. 0.5–1.0 mg); microdose 0.25 for tolerance Bottom line: the FDA ramp targets the maximum dose; community practice targets the lowest dose that keeps working, to minimize nausea and cost. Both use the same 4- week step cadence, never escalate faster. Nutrition & timing: protein first (1.2–1.6 g/kg/day), carbs last, to protect the lean mass these drugs burn with fat; lift 2–3×/wk + creatine 5 g/day. Stop eating ~3 h before bed (slowed emptying + lying flat drives reflux). Low intake favors mild ketosis, so a low-carb/keto approach pairs well; push water (2.5–3 L/day) + electrolytes, both dehydrate. |
| Contraindications | Personal or family history of medullary thyroid carcinoma (MTC) or MEN 2; personal/family history of any thyroid cancer Personal history of pancreatitis (any cause) Pre-existing gastroparesis or significant gastric motility disorder; severe GERD, scleroderma, or other delayed-emptying conditions Prior serious hypersensitivity to the compound or excipients Pregnancy and lactation; discontinue 2 months before planned conception. History of cholelithiasis / gallbladder disease. Active or pre-existing diabetic retinopathy; eating-disorder history; CKD stage 4–5 | |
| Warnings | Acute pancreatitis: discontinue if suspected (severe abdominal pain radiating to back) Acute gallbladder disease; diabetic-retinopathy progression; acute kidney injury from GI-related volume depletion (highest during escalation) NAION (non-arteritic anterior ischemic optic neuropathy), rare sudden monocular vision loss; EU label change 2025 Severe GI: ileus, obstruction, severe constipation, impaction. Anaphylaxis/angioedema reported. Tachycardia (1–4 bpm). Aspiration risk under anesthesia. | |
| Drug interactions | Delayed gastric emptying affects oral absorption (levothyroxine, oral contraceptives, warfarin); separate timing. Insulin / secretagogues: reduce at initiation. Do not combine with other GLP-1 agonists. | |
| Labs | Baseline: BMP/CMP, CBC, HbA1c, lipid panel, TSH, pregnancy test. BMP at every dose escalation and any time GI side effects cause >24h reduced intake. HbA1c at 3 + 6 mo; lipids at 6 mo; repeat eGFR if dehydration. Lipase if abdominal pain. Drop hsCRP / routine calcitonin., Out of range? Rising glucose/HbA1c = blood sugar creeping toward diabetes (recheck, tighten diet); a falling eGFR = kidney strain, usually dehydration (hydrate, hold the dose). | |
| Stop criteria | Creatinine rise >0.3 mg/dL or eGFR drop >20%: hold, rehydrate. Severe abdominal pain: evaluate for pancreatitis. Vision changes: ophthalmology. Persistent vomiting >48h: hold. New neck mass / hoarseness / dysphagia: thyroid workup. | |
| Patient education | acute kidney injury on GLP-1s is from dehydration, not the drug. Target 2.5–3 L water/day; hold next dose for any day of vomiting/diarrhea/reduced food; resume same level after 24h recovery. Required during any GLP-1 cycle: protein 1.2 g/kg IBW/day (1.6 if training), resistance training 2–3×/wk, creatine 5 g/day; else 25–40% of weight lost is lean mass with rapid regain. Eat slowly, stop at first fullness. Hold ≥1 week before general anesthesia/deep sedation (check current ASA position). Inform any anesthesiologist. Use contraception; discontinue ≥2 months before planned pregnancy. Pen sharing prohibited even with a new needle. | |
| References | rxlist · researchdosing · peptidedosages · DailyMed · PubMed · ClinicalTrials · GLP-1 sex differences · Jensterle 2020 |
