Semaglutide
FDA-approved GLP-1 receptor agonist · once-weekly subcutaneous
Semaglutide is the FDA-approved GLP-1 behind Ozempic and Wegovy, a long-acting copy of the gut hormone that signals fullness. People run it for weight loss and steadier blood sugar. In STEP-1 the 2.4 mg dose took off about 15% of body weight in 68 weeks.
At a glance
- Dose
- Start 0.25 mg, step up every 4 weeks toward 2.4 mg
- How often
- Once a week, same day
- How
- A small injection under the skin; a daily pill exists for diabetes
- When
- Any time of day; just hold the same weekday
- Ramp
- Step up slowly. The gradual ramp is what keeps nausea manageable
The 30-second versionEverything on this page, fast
Proven weight loss · Appetite control · Heart-protective · Once-weekly
The one that started the GLP-1 wave. Semaglutide (Ozempic / Wegovy) delivered ~15% average weight loss in trials, turns appetite down, steadies blood sugar and cut heart events ~20% in people with heart disease, all on one weekly shot.
The basics
- A peptide that copies the gut hormone GLP-1 to curb appetite and blood sugar.
- Sold as Ozempic / Rybelsus (diabetes) and Wegovy (weight loss).
Why people use it
- Real, trial-sized weight loss. About 15% of body weight at the top dose over ~68 weeks.
- Appetite turned down. A calorie deficit gets far easier to hold.
- Steadier blood sugar via glucose-dependent insulin and glucagon control.
- Heart-protective. Cut cardiovascular events ~20% in people with heart disease (SELECT).
Stacks well with
- Cagrilintide, the CagriSema pairing. A different satiety pathway for additive loss.
- Ipamorelin + CJC-1295, a GH nudge to protect lean mass while dieting.
Good to know
- Nausea and constipation are the common side effects. Worst while ramping, then they settle.
- Stop and the weight tends to return, so people run it long term.
- Some of the loss is muscle. Protein and lifting protect it.
What it does
- About 15% of body weight lostIn the STEP-1 human trial the 2.4 mg dose took off about 15% of body weight over 68 weeks.
- Appetite that finally goes quietIt acts on the brain's appetite centers and slows the stomach, so hunger and "food noise" drop.
- Steadier blood sugarIt raises insulin and lowers glucagon only when glucose is high, so it rarely causes lows on its own.
- Heart events cut by about 20%In the SELECT trial it cut major cardiovascular events by roughly 20% in people with established heart disease.
- One shot a weekA ~7-day half-life means one injection on a fixed day, far easier to keep than daily Liraglutide.
- Pairs cleanly with amylinIt works through GLP-1 alone, so it slots beside Cagrilintide (the CagriSema pairing) for additive weight loss.
Sources:PMID 33567185PMID 37952131PMID 27633186DailyMed (Wegovy)DailyMed (Ozempic)
How it works
Semaglutide switches on the GLP-1 receptor, the target of a gut hormone released after eating. One dose lasts about a week.
Quiets appetite. It acts on the brain's appetite centers, the hypothalamus and hindbrain, to cut hunger and food intake. This is the main driver of weight loss.
Slows the stomach. Food leaves the stomach more slowly, which blunts the blood-sugar spike after a meal and keeps you full longer. It is also where the nausea comes from.
Steadies blood sugar. It raises insulin and lowers glucagon only when blood sugar is high. The effect switches off at normal levels, so on its own it rarely causes low blood sugar.
Sources:DailyMed (Ozempic)PMID 27633186
How to dose it
A once-weekly injection under the skin. The dose starts low and steps up every 4 weeks to keep nausea down.
Dose tiersStart at 0.25 mg and step up every 4 weeks toward 2.4 mg.
- Weeks 1–4:
- 0.25 mg once weekly. A starter dose so the gut adapts.
- Weeks 5–8:
- 0.5 mg once weekly. Most people notice appetite dropping here.
- Weeks 9–12:
- 1.0 mg once weekly.
- Weeks 13–16:
- 1.7 mg once weekly.
- Week 17 onward (maintenance):
- 2.4 mg once weekly, the Wegovy maintenance dose (Ozempic tops out at 2 mg). People hold a lower step longer if the stomach complains.
How to injectOne injection into the fat under the skin, same day every week.
- Injection site:
- Abdomen (at least 2 inches from the navel), outer thigh or upper arm. Rotate sites each week.
- Pen (branded):
- Ozempic and Wegovy come as pre-filled pens. You dial the dose and inject.
- Research vial:
- 5 mg vial + 1 mL bacteriostatic water = 5,000 mcg/mL. On a U-100 syringe, 2.4 mg takes 48 units (0.48 mL) and 0.25 mg takes 5 units.
- Day of the week:
- People pick one day and hold it. About 7 days apart is the target. Up to a 3-day shift is fine.
Cycle and breaksPeople run it continuously, with no cycling.
- Ongoing use:
- Weight loss keeps building over 6–12 months. In SELECT the heart benefit accrued over ~4 years.
- On stopping:
- Weight tends to return. In the STEP extension most people regained much of it within a year of stopping.
- Dose holidays:
- Gaps of up to 2 weeks usually need no re-titration. After longer, people drop back one dose step and reclimb.
Mixing the vialThe calculator opens on the 2.4 mg maintenance dose. People ramp to it from 0.25 mg.
- Standard dilution:
- At 5 mg/mL, 0.25 mg takes 5 units, 0.5 mg 10 units, 1.0 mg 20 units, 1.7 mg 34 units and 2.4 mg 48 units on a 100-unit syringe.
- Why this dilution:
- The 2.4 mg maintenance dose takes 48 units (0.48 mL), a clean mid-syringe draw. The 0.25 mg starter takes 5 units.
Best time to take it
Implied best time
Anytime (consistent, same day weekly)
Most people take semaglutide on a fixed day each week. The day matters, the hour barely does.
- Its half-life is about 7 days, so blood levels stay nearly flat between doses. Holding one weekday keeps them steady.
- It works with or without food. Meal timing does not affect the injection.
- Early nausea is the main variable, so some people dose on a quiet weekend day when queasiness is least disruptive.
Sources:DailyMed (Ozempic)
What to stack it with
Semaglutide works only through GLP-1, so a second GLP-1 adds side effects and nothing else. Useful partners use a different pathway.
Semaglutide + Cagrilintide (CagriSema)The trial-backed pairing. Two satiety hormones, more weight loss.
- Why it works:
- Cagrilintide copies amylin, a satiety hormone that slows the stomach and cuts appetite through its own receptor, so effects add up.
- The protocol:
- Cagrilintide 2.4 mg SC once weekly beside the standard semaglutide ramp, same day, separate syringes. Cagrilintide has its own ramp. Also comes as a pre-mixed blend.
- Outcome:
- In phase 2 trials the pair beat either compound alone. People add it after a semaglutide plateau.
Semaglutide + Ipamorelin / CJC-1295A growth-hormone nudge that steers loss toward fat.
- Why it works:
- Ipamorelin and CJC-1295 trigger growth hormone pulses, which favor fat loss and muscle retention through a separate pathway.
- The protocol:
- Ipamorelin 200–300 mcg SC once daily at bedtime, with CJC-1295 no-DAC 100–200 mcg SC alongside, or CJC-1295 with DAC 2 mg SC once weekly. Add from week 5+.
- Outcome:
- More of the loss comes from fat. Suits people already lean or relying on muscle for sport.
Semaglutide + BPC-157Gut-lining support for the early, nausea-heavy weeks.
- Why it works:
- BPC-157 is studied for healing the gut lining. Semaglutide's stomach effects peak during the 0.25–1.0 mg steps.
- The protocol:
- BPC-157 250–500 mcg SC once daily for the first 8–12 weeks of the ramp, at an adjacent site. Taper once semaglutide sits well.
- Outcome:
- People add it for gut-lining support early on.
Sources:DailyMed (Wegovy)PMID 33567185
Support nutrients
These protect muscle, settle the stomach and fill nutrient gaps.
Protein, creatine and liftingThe top priority. Part of the weight lost is muscle.
- Protein target:
- 1.6–2.0 g per kg of body weight a day (roughly 0.7–0.9 g per pound), protein first at meals.
- Creatine:
- 3–5 g creatine monohydrate daily, any consistent time, no loading phase.
- Resistance training:
- 2–3 sessions a week of compound lifts (squat, hinge, push, pull).
Nausea and stomach upsetThe slow ramp does most of the work here.
- Ginger:
- 1–2 g with meals, as capsules, fresh or tea.
- Vitamin B6 (pyridoxine):
- 25–50 mg with meals on high-nausea days.
- Meal composition:
- Small, low-fat meals. Fatty food sits longest in the slowed stomach.
ConstipationSlower transit makes constipation common early in the ramp.
- Soluble fiber:
- 25–35 g total fiber a day, mostly soluble (oats, psyllium, legumes, fruit).
- Magnesium glycinate or citrate:
- 300–400 mg elemental magnesium at bedtime. It draws water into the colon.
- Hydration:
- 2–2.5 L of water a day, since less food means less fluid.
Electrolytes and micronutrientsEating much less means fewer minerals and vitamins coming in.
- Electrolytes:
- A supplement, or avocado, leafy greens, nuts and broth. Fatigue and cramps are the early signs.
- Daily multivitamin:
- A broad multivitamin. Watch B12, iron, calcium and vitamin D.
Gut microbiome supportSlower transit gives gut bacteria more time with food.
- Fermented foods and prebiotics:
- Daily yogurt, kefir, kimchi, sauerkraut or miso, plus garlic, onion, leeks, asparagus and oats. They feed the bacteria behind the body's own GLP-1.
Sources:DailyMed (Wegovy)PMID 33567185
Dose calculator
Reconstitution calculator
Calculated for a 1 mL U-100 insulin syringe (100 units/mL).
Units per dose
48 units
Draw this many units on a U-100 syringe
Each unit holds 50 mcg
- Volume per dose
- 0.48 mL
- Doses per vial
- 2
- Concentration
- 5 mg/mL
One vial lasts
- Daily
- 2 days
- Every other day
- 4 days
- 5×/week
- 2 days
- Large draw (48 units). That's normal for mg doses. To check it, multiply the units by what each unit holds. You should get your dose.
Research use only. Not for human consumption. Outputs are reference values based on research literature. Verify all measurements independently.
Side effects and what to watch
What people notice. Nausea, diarrhea, vomiting, constipation and abdominal pain. They scale with dose, hence the slow ramp.
How people handle it. People hold the ramp, eat small low-fat meals and keep up protein and lifting, since some loss is muscle. Weight tends to return after stopping.
Skip it or take care if. The label says to skip it with a personal or family history of medullary thyroid carcinoma (a thyroid cancer) or multiple endocrine neoplasia type 2 (MEN 2). It says to stop if pancreatitis is suspected, and lists gallbladder disease, kidney injury from dehydration, worsening diabetic retinopathy, and low blood sugar with insulin or sulfonylureas.
Competing? It is on the WADA Monitoring Program, tracked and not prohibited.
Common questions
How is semaglutide dosed?
Once a week under the skin. People start at 0.25 mg and step up every 4 weeks through 0.5, 1.0 and 1.7 mg to the 2.4 mg maintenance dose.
Why does the dose go up so slowly?
Nausea, diarrhea and vomiting scale with dose. Stepping up over weeks gives the gut time to adjust. The starter doses are for tolerability, and the full effect comes higher up the ladder.
Is it the same as Ozempic, Wegovy and Rybelsus?
Yes, all three are semaglutide. Ozempic is the weekly injection for diabetes, Wegovy the higher-dose weekly injection for weight loss, and Rybelsus the daily tablet.
How much weight do people lose?
In the STEP-1 trial the 2.4 mg weekly dose took off about 14.9% of body weight over 68 weeks, against 2.4% on placebo. Most people lost at least 5%.
Do I need to cycle it?
No. People run it continuously. Weight loss builds over 6–12 months, and most people regain much of the weight within a year of stopping.
What does it stack with?
Cagrilintide for more weight loss through a second satiety pathway. Ipamorelin with CJC-1295 to protect muscle. BPC-157 for gut-lining support during the ramp. A second GLP-1 adds nothing.
Deep dive
Doses used in studies · Molecular identity · References
10From the researchDoses used in studies
These are the doses used in the big human trials, including STEP-1 and SELECT. All were weekly injections or the daily oral tablet.
| Dose | Route | Model | Outcome | Sources: |
|---|---|---|---|---|
| 0.5 / 1.0 mg | SC weekly | Human (SUSTAIN-6, T2D high CV risk, n=3,297) | Major cardiac events 6.6% vs 8.9% placebo; HR 0.74 (noninferiority) | PMID 27633186 |
| 2.4 mg | SC weekly (68 wk) | Human (STEP-1, obesity, no diabetes, n=1,961) | Mean weight −14.9% vs −2.4% placebo; 86.4% lost ≥5% | PMID 33567185 |
| 2.4 mg | SC weekly (~40 mo) | Human (SELECT, overweight/obese + CVD, n=17,604) | Major cardiac events 6.5% vs 8.0%; ~20% relative risk reduction | PMID 37952131 |
| up to 14 mg | Oral daily | Human (PIONEER 6, T2D high CV risk, n=3,183) | Major cardiac events 3.8% vs 4.8%; HR 0.79, non-inferior | PMID 31185157 |
11ChemistryMolecular identity
- Molecular weight
- 4113.58 g/mol
- Molecular formula
- C187H291N45O59
- Monoisotopic mass
- 4111.12 Da
- Molecular target
- GLP-1 receptor (agonist)
- Amino acids
- 31-residue backbone (94% homology to GLP-1(7-37))FDA Ozempic label
- Structure / class
- Acylated GLP-1 receptor agonist; Aib8, Arg34, Lys26 C18-diacid via γGlu/miniPEG linkerFDA label; PubChem CID 56843331
- CAS / UNII
- 910463-68-2 · 53AXN4NNHXPubChem CID 56843331; FDA UNII
- Brand / approval
- FDA-approved as Ozempic & Rybelsus (T2D), Wegovy (weight management)FDA label
- Regulatory status
- FDA-approved drug; WADA 2026 Monitoring Program (monitored, not prohibited)FDA / WADA 2026
12Primary sourcesReferences
- PubChem CID 56843331PubChem CID 56843331 (Semaglutide, free acid)
- DailyMed (Ozempic)DailyMed, Ozempic (semaglutide) label
- DailyMed (Wegovy)DailyMed, Wegovy (semaglutide) label
- FDA NDA 213051FDA Rybelsus (oral semaglutide) label
- PMID 27633186Marso et al., NEJM 2016 (SUSTAIN-6, CV outcomes)
- PMID 33567185Wilding et al., NEJM 2021 (STEP-1, obesity)
- PMID 37952131Lincoff et al., NEJM 2023 (SELECT, CV outcomes)
- PMID 31185157Husain et al., NEJM 2019 (PIONEER 6, oral, CV outcomes)
- WADA 2026WADA 2026 Monitoring Program (GLP-1 agonists monitored, not prohibited)
Reviewed by Ki Researcher Team · Research use only · Not medical advice · Updated 2026-09-24