Semaglutide: The Most-Studied GLP-1
Semaglutide no longer has the biggest weight numbers in its class — tirzepatide passed it, and retatrutide's trial figures are larger still. It has something they do not: evidence that it changes what happens to people, not just what the scale reads. That distinction is the reason it remains the reference point for the entire category.
How it works
Semaglutide activates a single receptor, GLP-1. That slows gastric emptying, increases satiety and reduces food intake, with downstream effects on glycemic control. One receptor is why its weight numbers sit below the dual and triple agonists, and also why its mechanism is the best characterized in the class — it has been studied for longer and in more populations than anything else here.
What the evidence covers
Weight — STEP-1
1,961 adults, 68 weeks, published in the New England Journal of Medicine: semaglutide 2.4 mg produced a mean 14.9% weight reduction counting every randomized participant. This is the benchmark figure every subsequent obesity drug has been measured against.
Cardiovascular outcomes — the part that matters most
Semaglutide is approved to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight. That is a hard-outcome indication: evidence about heart attacks and strokes rather than about a surrogate marker. No other compound covered on this site has it, and no investigational compound can have it yet.
Liver disease
The label now also covers noncirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced liver fibrosis, under accelerated approval.
What happens after stopping
The STEP-1 trial extension followed participants after withdrawal and documented substantial weight regain. It is worth noting that the sponsor published this — the finding is unwelcome commercially and useful clinically, and it generalizes: there is no reason to expect any drug in this class behaves differently, including retatrutide, for which no discontinuation data exists at all.
Formulations and dosing
| Brand | Indication | Form |
|---|---|---|
| Wegovy | Weight management; cardiovascular risk reduction; noncirrhotic MASH with fibrosis | Injection, 0.25–7.2 mg dose strengths; also tablets |
| Ozempic | Type 2 diabetes | Injection |
| Rybelsus | Type 2 diabetes | Oral tablet |
Semaglutide is the only compound in this comparison with an oral formulation — a genuine pharmacological achievement for a peptide, which normally would not survive digestion. Dosing decisions belong with the prescribing physician.
Side effects
Gastrointestinal effects dominate — nausea, vomiting, diarrhea, constipation — worst during dose escalation. The label carries a boxed warning: semaglutide causes thyroid C-cell tumors in rodents at clinically relevant exposures, and whether it does so in humans is unknown. It is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2 syndrome. Pancreatitis, gallbladder disease and diabetic retinopathy complications also appear in the label.
How it compares
| Compound | Targets | Best result, counting everyone | Outcome data |
|---|---|---|---|
| Retatrutide | GIP + GLP-1 + glucagon | −25.0% at 80 weeks | None |
| Tirzepatide | GIP + GLP-1 | −20.9% at 72 weeks | Obstructive sleep apnea |
| Semaglutide | GLP-1 | −14.9% at 68 weeks | Major adverse cardiovascular events |
Read those two columns together. Ranking this class on weight alone puts semaglutide last; ranking it on demonstrated clinical benefit reverses the order. Detail inretatrutide vs semaglutide and the fullGLP-1 comparison table.
On compounded and research-grade semaglutide
Semaglutide spent years in shortage, during which compounded versions proliferated; FDA has since issued specific warnings about unapproved GLP-1 products sold for weight loss, including dosing errors and adverse event reports. Research-grade material sits further out still — unevaluated by any regulator, with no assurance the vial matches its label. An approved product exists for this molecule, which makes the trade clearer than it is for compounds that have no legal route at all.
Research on Semaglutide
9 records in our research database, classified by evidence type:
- HumanCoadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)Garvey WT et al. · New England Journal of Medicine, 2025
- HumanTirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)Aronne LJ et al. · New England Journal of Medicine, 2025
- HumanCagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)Davies MJ et al. · New England Journal of Medicine, 2025
- HumanWeight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extensionWilding JPH et al. · Diabetes, Obesity and Metabolism, 2022
Semaglutide — research vial — American Peptides
Research-use material, not the approved medicine. Approved prescription products exist for this molecule and come with a label, a pharmacist and a reviewed manufacturing process — none of which apply to research-grade vials.
We may earn a commission if you buy through this link (at no extra cost to you). Sold for research purposes only.
Frequently asked questions
What is semaglutide?
Semaglutide is a GLP-1 receptor agonist approved as Wegovy for weight management and cardiovascular risk reduction, as Ozempic for type 2 diabetes, and as Rybelsus in tablet form. It has the deepest evidence base of any drug in the incretin class.
How much weight do people lose on semaglutide?
In STEP-1, the pivotal 68-week obesity trial, semaglutide 2.4 mg produced a mean 14.9% reduction counting every randomized participant. Newer dual and triple agonists report larger figures, but none of them has semaglutide's outcome evidence.
Does weight come back after stopping semaglutide?
Yes. The STEP-1 trial extension followed participants after withdrawal and documented substantial regain. This is one of the most useful findings in the class, and it applies to the mechanism rather than to this drug specifically.
What is the semaglutide boxed warning?
Semaglutide causes thyroid C-cell tumors in rodents at clinically relevant exposures. Whether it does so in humans is unknown. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2 syndrome.
Is compounded or research-grade semaglutide the same as Wegovy?
No. Wegovy is a manufactured medicine with an FDA-reviewed process, a label and a traceable supply chain. FDA has issued specific warnings about unapproved and compounded GLP-1 products, including reports of dosing errors and adverse events.
Sources
- Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1). New England Journal of Medicine, 2021;384(11):989–1002. PubMed
- Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism, 2022;24(8):1553–1564. PubMed
- WEGOVY (semaglutide) prescribing information — indications, dose strengths, boxed warning. DailyMed label
- Drugs@FDA record for Wegovy. Drugs@FDA
- FDA. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. FDA
- Manufacturer self-pay pricing, checked 2026: Wegovy (NovoCare).
Related guides
- Tirzepatide: the approved dual agonist
- Retatrutide: the triple agonist in Phase 3
- Retatrutide vs semaglutide, compared honestly
- All GLP-1 drugs in one table
- Peptide reconstitution calculator