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Semaglutide

Studied for chronic weight management, type 2 diabetes glycemic control and cardiovascular risk reduction. A long-acting GLP-1 receptor agonist engineered by Novo Nordisk from human GLP-1, in clinical use since 2017 as Ozempic, Rybelsus and Wegovy.

categoryweight loss
clinical evidenceapproved
community adoptionvery high
uses graded6
sources12
last reviewed24 Aug 2026
compound file

The answer, first. A long-acting GLP-1 receptor agonist engineered by Novo Nordisk from human GLP-1, in clinical use since 2017 as Ozempic, Rybelsus and Wegovy. The strongest evidence is for chronic weight management, graded A — approval or replicated trials. Approved indication.

STEP 1: body weight fell 14.9% vs 2.4% on placebo at 68 weeks 1. At least 5% lost: 86.4% vs 31.5% 1. The pivotal record behind Wegovy.

What it is used for

Every use graded on its own evidence, not the compound as a whole. 6 outcomes, ranked by what the human record supports.

#outcome · human · animal · gradewhat the best evidence actually shows
01Chronic weight managementSTEP 1, n=1,961, 68 weeks · superseded by the human recordgrade AApproved indication. STEP 1: body weight fell 14.9% vs 2.4% on placebo at 68 weeks 1. At least 5% lost: 86.4% vs 31.5% 1. The pivotal record behind Wegovy.
02Type 2 diabetes glycemic controlSUSTAIN program, phase 3 · superseded by the human recordgrade AApproved as Ozempic and Rybelsus. SUSTAIN 1: HbA1c fell 1.45 to 1.55 points vs 0.02 on placebo over 30 weeks, n=387 dosed 2.
03Cardiovascular risk reductionSELECT, n=17,604 · superseded by the human recordgrade AApproved indication since 2024. SELECT: major cardiovascular events in 6.5% vs 8.0% on placebo over a mean 3.3 years, hazard ratio 0.80 3. SUSTAIN-6 found the same direction in diabetes 4.
04Chronic kidney disease in type 2 diabetesFLOW, n=3,533 · superseded by the human recordgrade AApproved for Ozempic in 2025. FLOW: major kidney events 24% lower, cardiovascular death 29% lower 5. The trial stopped early for efficacy 5.
05MASH with moderate to advanced fibrosisESSENCE part 1, n=800 · superseded by the human recordgrade AAccelerated approval 2025. ESSENCE week-72 interim: steatohepatitis resolved without fibrosis worsening in 62.9% vs 34.3% on placebo 6. The confirmatory arm runs to week 240 611.
06Alcohol use disorder [off-label]one RCT, n=48 · supportive rodent self-administration datagrade COne small RCT: fewer drinks per drinking day and lower craving at doses up to 1.0 mg over 9 weeks, n=48 7. Too small to change practice. No approval.
gradewhat it means
ARegulatory approval, or multiple adequately-powered trials agreeing with each other
BAt least one well-powered human randomised trial, with the direction replicated
CSmall or open-label human trials only
DAnimal or mechanism data only, with no controlled human outcome
EA claim the human trials have already killed

How it works

The proposed mechanism, in three steps. A mechanism is a reason to run a trial, never a substitute for one.

1targetAgonist at the GLP-1 receptor. Two amino-acid swaps plus a fatty-diacid chain make it albumin-bound and degradation-resistant 11.
2signalGlucose-dependent insulin secretion rises, glucagon falls, gastric emptying slows, and hypothalamic and hindbrain appetite circuits are engaged 11.
3effectAd libitum energy intake fell 24% across a day of test meals vs placebo, n=30, after 12 weeks at 1.0 mg 8.

What it does not do

Claims the current record does not support. Worth knowing before you set expectations.

not supported by the evidence

How it is used

What published protocols administered, and what the community reports doing. Descriptive on both counts, and never a recommendation.

routeOnce-weekly subcutaneous injection in abdomen, thigh or upper arm. Daily oral tablets exist as Rybelsus and oral Wegovy 1112.
formatPrefilled pens and tablets as the approved product. Lyophilized gray-market vials otherwise.
published dosesWegovy label: 0.25 mg weekly, stepped every 4 weeks to 1.7 or 2.4 mg maintenance 11. Ozempic: 0.25 to 0.5 mg, then 1 or 2 mg weekly 12. STEP 1 dosed 2.4 mg after a 16-week escalation 1.
human pharmacokineticsElimination half-life about one week. Drug is present 5 to 7 weeks after the last 2.4 mg dose 11.
reported conventionsAs reported on r/semaglutide, r/Peptides and group-buy threads, 2022-2026: gray-market vials reconstituted with bacteriostatic water, drawn in insulin-syringe units. Escalation is copied from the label ladder. Some users hold low doses for cost or maintenance. Convention, not guidance.
commonly paired withCagrilintide

This site does not publish protocols to follow. The doses above are what studies administered or what users report, stated as facts about the literature and the market. How protocols are structured, mixing and storage and the reconstitution calculator cover the arithmetic.

What to expect

Where a trial measured it, the trial. Where only the community reports it, that is said out loud.

onsetSTEP 1: the weight curve separated from placebo during the first month and reached its 14.9% mean at week 68 1. The label ladder itself takes 16 weeks to reach the 2.4 mg maintenance dose 11.
most common reportAs reported: appetite and food noise quiet within the first weeks at low doses. The scale moves more slowly than the appetite does.
adverse effectsSTEP 1: nausea and diarrhea most common, typically transient and mild to moderate 1. Stopping for gastrointestinal events ran 4.5% vs 0.8% 1. SELECT: 16.6% vs 8.2% discontinued for adverse events 3. As reported: escalation weeks are the worst.
the stop signalLabel: discontinue for suspected pancreatitis 11. Contraindicated with personal or family medullary thyroid carcinoma or MEN2 history 11. As reported: vomiting that will not settle, or dehydration, is the community stop signal.

Approval and status

What regulators and sport bodies have actually said, separately from what the evidence shows.

approvalFDA-approved as Ozempic [2017], Rybelsus [2019] and Wegovy [2021]. Indications span diabetes, weight, cardiovascular risk, kidney disease and MASH.
FDAApproved products only. The shortage-era compounding pathway closed in 2025. Research-market vials are unapproved, and bulk GLP-1 imports face default detention under Import Alert 66-80.
sport [WADA]Not on the WADA Prohibited List. GLP-1 agonists are not banned in sport.
sold asapproved medicine

Covered in depth

These reports grade Semaglutide at length and carry their own verified reference lists.

How much muscle you lose

Roughly a quarter to a third of the weight lost on GLP-1 agonists can be lean mass. The trial data, the resistance-training counterweight, and the protein math.

Check the vial

The grade above describes a molecule studied under controlled conditions. It says nothing about the powder in a particular vial.

That gap is the one part of this market a reader can actually close. How to read a certificate of analysis covers the five measures in five minutes, and the 2026 audit grades vendors on the documents they publish against a rubric printed in full.

Questions we get

What is Semaglutide used for?

Five approved lanes 1235611. Chronic weight management, type 2 diabetes, cardiovascular risk reduction in established heart disease.

Chronic kidney disease in diabetes, and noncirrhotic MASH with F2 to F3 fibrosis. Each approval names an indication, a dose and a product. Off-label, one small RCT supports further study in alcohol use disorder, n=48 7. Community use tracks the weight indication almost entirely.

How is Semaglutide used?

The label describes once-weekly subcutaneous injection. For weight, 0.25 mg escalated every 4 weeks to 1.7 or 2.4 mg 11.

For diabetes, 0.5 to 2 mg 12. Daily oral tablets also exist. As reported on gray-market forums, vials are reconstituted and dosed in insulin-syringe units mirroring that ladder. Descriptive only. Convention, not guidance.

How long does Semaglutide take to work?

Reaching the full 2.4 mg dose takes 16 weeks by label 11. In STEP 1 the weight curve separated from placebo during the first month of escalation 1.

It was still falling past week 60, ending at 14.9% down at week 68 1. Appetite effects are reported earlier than scale effects. Withdrawal reverses it: two-thirds of lost weight returned within a year off drug 9.

Is Semaglutide an approved drug?

Yes, for specific indications. An approval attaches to a named indication, a named dose and a manufactured product. It does not extend to a research-market vial, an off-label goal, or a dose worked out on a forum.

On our index it is graded approved on clinical evidence and very high on community adoption, and those two are rated separately on purpose.

Does Semaglutide cause muscle loss?

In STEP 1's DXA substudy roughly 39% of the weight lost was lean mass 1. Lean mass is not all muscle.

The compartment includes water and organ tissue, and all rapid weight loss takes some. The counterweights with evidence are resistance training and protein around 1.6 to 2.2 g per kg per day. Our GLP-1 muscle report covers the numbers in full.

References

  1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity [STEP 1]. N Engl J Med. 2021. PMID 33567185
  2. Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes [SUSTAIN 1]. Lancet Diabetes Endocrinol. 2017. PMID 28110911
  3. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes [SELECT]. N Engl J Med. 2023. PMID 37952131
  4. Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes [SUSTAIN-6]. N Engl J Med. 2016. PMID 27633186
  5. Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes [FLOW]. N Engl J Med. 2024. PMID 38785209
  6. Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis [ESSENCE]. N Engl J Med. 2025. PMID 40305708
  7. Hendershot CS, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025. PMID 39937469
  8. Blundell J, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017. PMID 28266779
  9. Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022. PMID 35441470
  10. Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity [SURMOUNT-5]. N Engl J Med. 2025. PMID 40353578
  11. Wegovy [semaglutide] Prescribing Information, current label. Novo Nordisk. 2026. dailymed.nlm.nih.gov
  12. Ozempic [semaglutide] Prescribing Information. Novo Nordisk. 2026. dailymed.nlm.nih.gov

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