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.
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.
What the research shows
- 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).
Evidence labels: 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.
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.
Dosing and protocol
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.
Ongoing. Weight regain is the norm after stopping, so plan for long-term use or a slow taper.
Same day each week, any time of day, with or without food. Rotate injection sites between abdomen, thigh and upper arm.
| 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 |
Lyophilized: fridge 2-8C away from light, freezer for long-term. Reconstituted: fridge 2-8C, use within 4 weeks. Do not freeze once mixed.
Cautions
- ▲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.
Commonly stacked with
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