Semaglutide
Sema · Ozempic · Wegovy · Rybelsus · NN9535
Long-acting GLP-1 agonist dosed weekly; the reference compound for appetite-driven fat loss.
Typical dose
1 mg
Once weekly
Range
0.25–2.4
mg
Half-life
7 days
see Dosing
Evidence
Human trials
Subcutaneous · Oral
What it is
Semaglutide is a GLP-1 receptor agonist built from the human GLP-1 backbone, modified with an Aib substitution and a C18 diacid fatty chain that binds albumin. That modification is what turns a peptide with a two-minute native half-life into one dosed once a week.
It is approved for type 2 diabetes (Ozempic, Rybelsus) and for weight management (Wegovy). In the STEP 1 trial, 2.4 mg weekly produced roughly 15% mean body weight loss over 68 weeks against about 2.4% on placebo. It is the compound most other incretins get benchmarked against.
In a bodybuilding context it is used almost entirely as an appetite tool: it makes a deficit tolerable rather than burning fat directly. The trade-off is that a meaningful share of the weight lost is lean tissue unless training volume and protein intake are held up deliberately.
Grey-market lyophilised semaglutide is widely sold and is chemically the same molecule, but purity and actual mg content vary by source. Third-party testing is the only way to know what is in a vial.
How it works
Semaglutide activates GLP-1 receptors in the hypothalamus and brainstem, which raises satiety signalling and lowers the drive to eat. It also slows gastric emptying, so food sits in the stomach longer and meals feel larger than they are. The combined effect is a large, sustained drop in spontaneous calorie intake.
In the pancreas it increases glucose-dependent insulin secretion and suppresses glucagon, which is why it lowers blood sugar without much hypoglycaemia risk on its own. The albumin-binding fatty acid chain and DPP-4 resistance from the Aib substitution give it a roughly week-long half-life, so plasma levels stay flat between injections.
Dosing
Nobody starts at 1 mg. Everyone titrates from 0.25 mg with roughly 4 weeks at each step, and the ceiling is 2.4 mg weekly for weight management (2 mg for the diabetes label). Every number in this entry is for the subcutaneous route only. Oral semaglutide is a separate product on a separate schedule — 3-14 mg once daily as Rybelsus, with a higher-dose 25 mg once-daily tablet for weight management — and none of the vial, reconstitution or weekly-dose figures here apply to it.
Standard titration
| Step | Dose | Note |
|---|---|---|
| Weeks 1-4 | 0.25 mg | Tolerance-building dose, not expected to drive much weight loss |
| Weeks 5-8 | 0.5 mg | First dose where appetite suppression is usually obvious |
| Weeks 9-12 | 1 mg | Common long-term maintenance dose; many people stop here |
| Weeks 13-16 | 1.7 mg | Only escalate if weight loss has genuinely stalled |
| Week 17 onward | 2.4 mg | Label maximum for weight management; side effects scale with dose |
Reconstitution calculator
Pre-loaded with Semaglutide’s vial size, water volume and typical dose. Change anything.
Typical: 1 mg · range 0.25–2.4
Draw to
40 u
0.4 mL · 1 mg
Concentration
2.5 mg/mL
25 mcg per unit
Doses per vial
5
Vial lasts
5 weeks
Draw to 40 units on the barrel.
Once mixed
Refrigerate at 2-8C and use within about 4-6 weeks; discard sooner if the solution turns cloudy or shows particles. This vial would take about 5 weeks to finish — check that against the storage window before mixing the whole thing.
A 5 mg vial with 2 mL bacteriostatic water gives 2.5 mg/mL, so 0.25 mg is 10 units on a U-100 insulin syringe and 2.4 mg is 96 units. Add the water slowly down the inside wall, then swirl or roll the vial; do not shake, as agitation denatures the peptide and causes foaming.
Storage
Before mixing
Refrigerated at 2-8C the sealed powder is stable for years; it tolerates several weeks at room temperature during shipping, but keep it dark and dry.
After mixing
Refrigerate at 2-8C and use within about 4-6 weeks; discard sooner if the solution turns cloudy or shows particles.
Reported benefits
- ▪Large, reliable drop in appetite and food preoccupation
- ▪Roughly 15% mean body weight loss over 68 weeks at 2.4 mg in trial conditions
- ▪Once-weekly dosing with flat plasma levels and no timing pressure
- ▪Improves HbA1c, fasting glucose and insulin sensitivity
- ▪Reduced major cardiovascular events in both diabetic and non-diabetic obese populations
- ▪Lowers blood pressure and triglycerides alongside the weight loss
Side effects
- ▪Nausea, vomiting, diarrhoea and constipation, worst in the first weeks after each dose increase
- ▪Sulphurous burps and reflux from delayed gastric emptying
- ▪Significant lean mass loss if protein and resistance training are not maintained
- ▪Fatigue and reduced training capacity from low calorie intake, not from the drug itself
- ▪Gallstones, driven mainly by the rate of weight loss
- ▪Acute pancreatitis, rare but documented
- ▪Loss of appetite so complete that hitting a protein target becomes the limiting factor
- ▪Markedly delayed gastric emptying — the stomach can still hold solid food many hours after a meal, so any surgery, endoscopy or procedural sedation needs the drug held beforehand and the anaesthetist told, because of the aspiration risk from retained gastric contents.
Do not use if
- ▪Personal or family history of medullary thyroid carcinoma or MEN2 syndrome
- ▪History of pancreatitis
- ▪Gastroparesis or other significant gastric motility disorder
- ▪Pregnancy or trying to conceive; wash out at least 2 months beforehand given the half-life
- ▪Type 1 diabetes as a substitute for insulin
Evidence level — Human trials
Controlled human clinical data exists.
FDA- and EMA-approved as a prescription drug (Ozempic, Wegovy, Rybelsus); lyophilised vials sold outside that channel are unlicensed research-chemical supply.
Commonly run with
Cagrilintide
Long-acting amylin analogue run weekly for satiety, usually alongside a GLP-1.
2.4 mg · once weekly
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
Tesamorelin
The only FDA-approved GHRH analogue, proven to shrink visceral abdominal fat.
2 mg · once daily
HGH
Recombinant human growth hormone, the reference compound every GH peptide tries to imitate.
2 IU · Once daily, split into two injections above about 4 IU
5-Amino-1MQ
Oral NNMT inhibitor aimed at fat-cell metabolism and NAD+ salvage. Mouse data only.
100 mg · once daily
Semaglutide FAQ
Will I lose muscle on semaglutide?+
Yes, some. Trial data show roughly 30-40% of the total weight lost is lean mass, which is broadly what any large deficit produces. Keeping protein around 2 g/kg and holding your resistance training volume is what changes that number, not the dose.
What happens when I stop?+
Appetite returns over about 4-6 weeks as the drug clears, and the STEP 1 extension showed participants regained roughly two thirds of the lost weight within a year off drug. It is a tool for building eating habits during the window it is working, not a fix on its own.
Can I run it while bulking or on cycle?+
People do use low doses (0.25-0.5 mg) to blunt appetite on a lean bulk or to manage glucose while on high-dose anabolics. It works, but at any dose it slows gastric emptying, which makes hitting a surplus genuinely hard.
Why did the nausea come back after weeks of being fine?+
Almost always a dose increase. GI side effects reset with each titration step and typically settle within one to two weeks. If they do not, drop back to the previous step and hold there longer rather than pushing through.
Is grey-market semaglutide the same molecule?+
Chemically it can be identical, since the synthesis is well documented. What varies is purity, actual mg per vial, and residual solvents. Anything without a recent third-party HPLC and mass spec report on that specific batch is unverified.
References
- 1.Once-Weekly Semaglutide in Adults with Overweight or Obesity — New England Journal of Medicine (2021) PMID 33567185
- 2.Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes — New England Journal of Medicine (2023) PMID 37952131
- 3.Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes — New England Journal of Medicine (2016) PMID 27633186
Related reading
More fat loss & metabolic
5-Amino-1MQ
Oral NNMT inhibitor aimed at fat-cell metabolism and NAD+ salvage. Mouse data only.
100 mg · once daily
AOD-9604
Modified hGH tail fragment sold for lipolysis without the IGF-1 rise of growth hormone.
300 mcg · once daily
Cagrilintide
Long-acting amylin analogue run weekly for satiety, usually alongside a GLP-1.
2.4 mg · once weekly
HGH Fragment 176-191
The C-terminal tail of growth hormone, sold for fat loss on almost entirely rodent evidence.
250 mcg · Once daily, fasted (many split it into two 250 mcg doses)