Semaglutide
Also known as Ozempic, Wegovy, Rybelsus, NN9535
Semaglutide is a once-weekly GLP-1 receptor agonist that cuts appetite and slows digestion, producing average weight loss around 15 percent in trials. It is the molecule behind the Ozempic and Wegovy brand names.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 0.25 mg (starting dose)
- How often
- once weekly
- Where
- Subcutaneous, abdomen, thigh or upper arm, rotate sites
- Timing
- same day each week, any time, with or without food
- Effects timeline
- appetite drops within 1 to 2 weeks, steady weight loss from about week 4 once past 0.5 mg, plateau around 12 to 18 months
- Storage
- fridge 2 to 8 C once mixed, use within 4 weeks
- Cycle length
- ongoing, step up every 4 weeks through 0.5, 1.0, 1.7 and 2.4 mg
- Break between
- none planned; if stopping, taper down over a few months rather than quitting cold
0.25 mg is a tolerance dose, not a treatment dose. Maintenance is usually 1.0 to 2.4 mg weekly, and the right level is the lowest step that keeps appetite controlled with tolerable nausea.
Overview
Semaglutide is a modified version of the gut hormone GLP-1, engineered by Novo Nordisk so that it survives in the bloodstream for about a week instead of a few minutes. A fatty acid chain lets it ride on albumin, and two amino acid swaps protect it from the enzyme that normally chops GLP-1 apart. It was first approved for type 2 diabetes as Ozempic in 2017, then for chronic weight management as Wegovy in 2021. A daily tablet form exists as Rybelsus.
The weight loss evidence is about as strong as it gets for anything on this site. In the STEP 1 trial, adults without diabetes who took 2.4 mg weekly for 68 weeks lost an average of about 15 percent of body weight, compared with roughly 2.5 percent on placebo. The SELECT trial later showed a 20 percent reduction in major cardiovascular events in people with obesity and existing heart disease, which led the FDA to add a cardiovascular indication.
One thing to be clear about: the vials sold by research suppliers and the compounded versions from pharmacies are not the same product as the branded pens, even when the molecule is nominally identical. Branded pens come from a regulated manufacturer with lot testing and a known concentration. Grey-market lyophilized powder may or may not contain what the label says, and purity varies by source. If you go that route, third-party testing of the specific batch is the only way to know what you actually have.
How it works
Semaglutide activates GLP-1 receptors in the pancreas, gut and brain. In the pancreas it increases insulin release when glucose is high and suppresses glucagon, which improves blood sugar control. In the stomach it slows emptying, so meals feel filling for longer. The effect people notice most comes from the brain: receptors in the hypothalamus and brainstem reduce hunger signals and the reward value of food, so smaller portions feel like enough and the constant background thinking about food quiets down. Because the molecule is bound to albumin it releases slowly, and one weekly injection keeps blood levels steady.
Where the research stands
Chronic weight managementStrong evidence
- Obesity without diabetes. STEP 1 RCT, about 15 percent mean loss at 2.4 mg over 68 weeks.
- Overweight with type 2 diabetes. STEP 2 RCT, about 10 percent loss, less than in non-diabetics.
- Adolescent obesity. STEP TEENS RCT led to approval in ages 12 and up.
Type 2 diabetesStrong evidence
- Glucose control. SUSTAIN program RCTs, HbA1c reductions of 1 to 1.8 points, the basis of the Ozempic approval.
- Oral tablet option. PIONEER RCTs support Rybelsus for people who will not inject.
Cardiovascular riskStrong evidence
- Heart attack and stroke prevention. SELECT RCT, 20 percent fewer major cardiovascular events in obesity with existing heart disease.
- Heart failure with preserved ejection fraction. STEP-HFpEF RCT improved symptoms and exercise capacity.
Kidney diseaseModerate evidence
- Diabetic kidney disease progression. FLOW RCT reduced major kidney outcomes by about 24 percent in type 2 diabetes with chronic kidney disease.
Fatty liver diseaseModerate evidence
- Steatohepatitis (MASH). ESSENCE phase 3 RCT showed resolution of steatohepatitis in a majority on 2.4 mg, with fibrosis improvement.
- human RCT2.4 mg weekly produced about 15 percent mean weight loss over 68 weeks in adults with obesity (STEP 1).
- human RCTReduced major adverse cardiovascular events by 20 percent in people with overweight or obesity and established heart disease (SELECT).
- clinical (approved drug)Lowered HbA1c and cardiovascular risk in type 2 diabetes (SUSTAIN-6), the basis for the original Ozempic approval.
- human RCTMost of the lost weight returned within a year of stopping in the STEP 1 extension.
- human RCTOral semaglutide at 50 mg daily produced weight loss similar to the 2.4 mg injection (OASIS 1).
Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Levels over time
Modeled from the half-life. Illustrative, not measured.Dosing every 7 d with a half-life of 6.9 d means each dose lands on top of what is left from the last one. Levels climb to about 2.0 times a single dose before settling, roughly 27.5 d in.
The week-long half-life is why one injection a week gives steady levels, and why each dose step takes about a month to fully settle before the next increase makes sense.
Semaglutide dosage and protocols
Not cycled. The label schedule is a slow titration with each step held for 4 weeks, and people who tolerate a step well often stay there rather than climb. Stopping is done as a gradual taper because appetite and weight return quickly after abrupt withdrawal.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Weeks 1 to 4, tolerance | 0.25 mg | once weekly | Subcutaneous |
| Weeks 5 to 8 | 0.5 mg | once weekly | Subcutaneous |
| Weeks 9 to 12 | 1.0 mg | once weekly | Subcutaneous |
| Weeks 13 to 16 | 1.7 mg | once weekly | Subcutaneous |
| Week 17 onward, maintenance | 2.4 mg, or the lowest step that works | once weekly | Subcutaneous |
Food and time of day do not matter for the injection. Many people inject in the evening so the first day of peak nausea is spent asleep. Keep the day of the week consistent; a missed dose can be taken up to 5 days late, otherwise skip it. Do not step up while still nauseous on the current dose.
Start 0.25 mg weekly, step up every 4 weeks (0.25, 0.5, 1.0, 1.7, 2.4 mg). Many people stop escalating at whatever dose controls appetite rather than pushing to the top.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 5 mg | 1 mL | 5 mg/mL | 5 units |
| 10 mg | 1 mL | 10 mg/mL | 2.5 units |
| 20 mg | 2 mL | 10 mg/mL | 2.5 units |
How to reconstitute Semaglutide
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1 to 4
Mild appetite reduction, some nausea and fullness after small meals. Little weight change at 0.25 mg.
- Week 4 to 12
Appetite clearly suppressed as the dose climbs, food noise quiets, loss of roughly 1 to 2 pounds a week is typical.
- Month 3 to 6
Steady loss continues at maintenance dose, side effects mostly settle, clothes size drops.
- Month 6 to 18
Rate slows and plateaus, usually near 15 percent of starting weight. Muscle and protein intake become the focus.
Interactions and stacking
Cagrilintidesynergistic
Amylin adds a separate satiety signal; the CagriSema combination outperformed semaglutide alone in phase 3.
Tirzepatideavoid
Two long-acting incretin agonists at once stack GI effects with no evidence of added benefit; pick one.
Retatrutideavoid
Same reasoning, overlapping GLP-1 activity and compounded nausea with nothing gained.
Insulin and sulfonylureascaution
Semaglutide alone rarely causes low blood sugar, but combined with these it can; doses of the other drug usually need to come down.
Oral medications with a narrow margincaution
Slower stomach emptying can change absorption of drugs like warfarin, levothyroxine and some antiepileptics, so monitoring matters during titration.
Ipamorelin and other ghrelin mimeticscompatible
No pharmacological conflict, but ghrelin mimetics raise hunger and can partly work against appetite suppression.
MOTS-ccompatible
Community pairing to support exercise capacity during weight loss; no combined data.
Alcoholcaution
Tolerance drops noticeably, and alcohol worsens nausea, reflux and dehydration on top of the effects of the drug itself.
Safety
- ▲Nausea, especially the first few days after each dose increase
- ▲Constipation or diarrhea
- ▲Burping, reflux and early fullness
- ▲Fatigue and low energy from eating less
- ▲Injection site redness or itching
- ▲Hair shedding a few months into rapid weight loss
- ▲Nausea, vomiting, constipation and diarrhea are common, especially in the first weeks after each dose increase. Escalating too fast is the number one mistake.
- ▲Boxed warning for thyroid C-cell tumors seen in rodents. Avoid with a personal or family history of medullary thyroid cancer or MEN2.
- ▲Pancreatitis and gallbladder problems are rare but real. Severe persistent abdominal pain means stop and get checked.
- ▲Rapid weight loss takes lean mass with it. Protein intake and resistance training matter.
- ▲Slowed stomach emptying is relevant before surgery or anesthesia. Tell your anesthesiologist.
- ■Severe, persistent abdominal pain, with or without vomiting, which can signal pancreatitis
- ■Pain under the right ribs, yellowing skin or eyes, or pale stools, which point to gallbladder problems
- ■Vomiting that prevents keeping fluids down for more than a day
- ■A lump in the neck, hoarseness or trouble swallowing
- ■Vision changes if you have diabetes, since rapid glucose improvement can worsen retinopathy
Community poll
Self-reported by visitors. Not clinical evidence.Semaglutide: frequently asked
How much weight do people lose on semaglutide?
In the main obesity trial, average loss at the 2.4 mg dose was about 15 percent of starting body weight over 68 weeks. Roughly a third of participants lost 20 percent or more, and some lost very little. Response varies a lot from person to person.
What happens when you stop?
Appetite comes back, usually within a few weeks, and most people regain the majority of the weight within a year. Some people manage this with a slow taper to a lower maintenance dose, but there is no reliable way to lock in the loss without continued treatment or a permanent change in habits.
Is a compounded or research vial the same as Wegovy?
The active molecule should be the same, but the product is not. Branded pens are manufactured under FDA oversight with verified concentration. Compounded products vary by pharmacy, and research-grade vials have no guaranteed purity unless you test them. Dosing errors are also far more common when people draw from vials.
How do I convert milligrams to units on an insulin syringe?
It depends entirely on how much bacteriostatic water you add. A 5 mg vial mixed with 2 mL gives 2.5 mg per mL, so 0.25 mg is 0.1 mL, which is 10 units on a U-100 syringe. Use the site's reconstitution calculator rather than doing it in your head.
Does semaglutide cause muscle loss?
Any large weight loss includes some lean mass, and trial body composition data suggest roughly a quarter to a third of the weight lost is lean tissue. That is not unique to the drug. Eating enough protein and lifting weights shifts the ratio toward fat loss.
References
- Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine, 2021
- Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine, 2023
- Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). New England Journal of Medicine, 2016
- Weight regain and cardiometabolic effects after withdrawal of semaglutide (STEP 1 extension). Diabetes, Obesity and Metabolism, 2022
- Oral semaglutide 50 mg once daily in adults with overweight or obesity (OASIS 1). The Lancet, 2023