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Weight loss

Semaglutide

GLP-1 receptor agonist · NN9535

ApprovedReviewed 12 Aug 2026

Semaglutide is a synthetic analogue of glucagon-like peptide-1 (GLP-1), a hormone the gut releases after eating. Structural changes to the natural peptide, including a fatty-acid chain that binds it to albumin in the blood, extend its half-life from minutes to roughly a week. That is what makes weekly dosing possible.

It is among the most thoroughly studied compounds described anywhere on this site. Large randomised trials have measured its effects on blood glucose, body weight and cardiovascular outcomes, and it holds regulatory approval in multiple jurisdictions. That places it in a different evidence category from most research peptides, and the profile below reflects that.

The corollary is worth stating plainly: material bought as a research chemical is not the approved medicine. The trials below tested a product manufactured to pharmaceutical standard, with a known quantity of a known substance in each vial. That is the thing being evidenced, and it is not what is being sold on the gray market.

How it works

GLP-1 receptors sit in the pancreas, the stomach, and parts of the brain that regulate appetite. Activating them prompts the pancreas to release insulin when blood glucose is high, suppresses glucagon, and slows the rate at which the stomach empties.

The appetite effect appears to be largely central rather than digestive: receptor activity in the hypothalamus and brainstem reduces hunger and increases the sense of fullness after a smaller meal. The slowed gastric emptying contributes, and is also the source of the nausea commonly reported in trials, particularly while a dose is being increased.

Regulatory status — United States

Approved by the FDA as a prescription medicine for type 2 diabetes and for chronic weight management. Material sold as a research chemical is not the approved product — is not manufactured to the same standard — and is not legal to sell for human use.

Last reviewed 12 Aug 2026. Regulatory positions in this category change frequently; we date this line so you can see how current it is.

What it is studied for

Each entry states the evidence behind it. We do not rank indications by effectiveness — for most compounds here, that would be a claim nobody can support.

Weight management

Clinical trial

Approved for chronic weight management alongside diet and activity.

EvidenceLarge randomised placebo-controlled trials in adults with obesity, run over 68 weeks.

Type 2 diabetes

Clinical trial

Approved for glycaemic control in type 2 diabetes.

EvidenceMultiple phase 3 trials.

Identity and clearance

Molecule

Class
GLP-1 receptor agonist, acylated analogue
Molecular weight
4113.58 Da
Length
31 amino acids

A modified GLP-1 backbone with a C18 fatty diacid chain. That chain binds albumin in the blood. That is what slows clearance enough for weekly dosing.

Pharmacokinetics

Clinical trial
Peak24 h
Half-life7 d
Substantially cleared5 w
100%50%25%0%half-life 7ddose8.8d3w4w5w
Modelled from the half-life above, assuming first-order elimination. Illustrative rather than measured — it shows the shape of clearance, not a prediction for any individual.

A half-life near seven days means roughly five weeks pass before a dose is substantially cleared, and that any dose change takes weeks to show its full effect.

Dose protocols reported in sources

Displayed for reference only. Every row says where it came from, and a trial protocol and a community convention are not the same kind of information. None of this is fed into the calculator, and none of it is a recommendation.

Dose protocols reported in sources, with the source of each.
GoalDoseFrequencyRouteUnits, 3 mg vialSourceStart this protocol
Trial escalation, weeks 1–4250 mcgOnce weeklySubcutaneous8.33 uClinical trialStart this
Trial escalation, weeks 5–16500 mcg – 1.7 mgOnce weekly, raised in steps every four weeksSubcutaneous16.67–56.67 uClinical trialStart this
Trial maintenance dose2.4 mgOnce weeklySubcutaneous80 uClinical trialStart this

Start this copies a row into a protocol of your own, which you can then edit. Where a source gave a dose range or an ambiguous frequency, those fields arrive empty — we will not pick a number on your behalf.

Calculator

Work out what to draw

Pre-filled with a 5 mg vial as a worked example. These are not recommended values — change them to match the vial in front of you.

Dose unit
Your syringe
010203040506070809010010 units0.1 mL

Draw to 10 units on a 1 mL U-100 syringe. That is 0.1 mL, containing 250 mcg of Semaglutide.

Concentration2.5mg / mL
Volume drawn0.1mL
Doses per vial20doses
Per unit25mcg / unit

10 units sits exactly on a printed line.

Bioalmanac performs arithmetic on values you enter. It does not recommend doses, schedules or compounds, and nothing here is medical advice. Confirm every calculation against your vial and syringe before drawing, and speak with a licensed healthcare provider.

Open this calculation in the full calculator

Units, concentration, bacteriostatic water — the glossary defines the vocabulary, and a unit is not a fixed volume.

Safety

Reported effects

  • NauseaClinical trial

    Very common in trials

    The most frequently reported effect, worst in the days following a dose increase and usually settling as the dose is held.

  • Diarrhoea, constipation, vomitingClinical trial

    Common in trials

  • Reduced appetite and early fullnessClinical trial

    Very common

    The intended effect, but it can go far enough to make adequate protein and fluid intake difficult.

  • Gallbladder problems, including gallstonesClinical trial

    Uncommon but documented

    Associated with rapid weight loss generally as well as with the drug itself.

  • PancreatitisClinical trial

    Rare

    Severe, persistent abdominal pain radiating to the back is the presentation to act on.

  • Loss of lean mass alongside fatClinical trial

    Documented in trials

    A substantial share of weight lost can be lean tissue. Resistance training and adequate protein are the usual countermeasures.

When to stop

  • Severe, persistent abdominal pain, especially radiating to the back and with vomiting. That is the presentation of pancreatitis. Seek urgent medical care.
  • Persistent vomiting or inability to keep fluids down. Dehydration is the most common route to serious trouble on these drugs.
  • Signs of gallbladder disease: pain in the upper right abdomen, fever, or yellowing of the skin or eyes.
  • A lump or swelling in the neck, hoarseness, or difficulty swallowing.
  • Any allergic response: rash, hives, facial swelling, or difficulty breathing. Seek urgent care.
  • If you become pregnant or are planning to.

Interactions and situations that need care

  • Personal or family history of medullary thyroid carcinoma, or MEN 2Avoid

    The approved products carry a boxed warning on this basis, following thyroid C-cell tumours in rodent studies.

  • History of pancreatitisUse caution

    Pancreatitis is a documented if uncommon adverse event, and prior episodes raise the stakes of another.

  • Pregnancy and breastfeedingAvoid

    Not recommended in pregnancy. Given the long half-life, trial protocols called for stopping well in advance of a planned conception.

  • Insulin or sulfonylurea therapyUse caution

    Combining glucose-lowering agents raises hypoglycaemia risk, and doses of the other agent often need adjusting by whoever prescribes them.

  • History of eating disordersUse caution

    A drug whose primary effect is appetite suppression interacts with restrictive eating patterns in ways that warrant clinical oversight rather than self-management.

  • Planned surgery or general anaesthesiaUse caution

    Delayed gastric emptying means the stomach may not be empty after standard fasting, which is an aspiration risk under anaesthesia. Tell your anaesthetist.

What to expect

  • In the STEP 1 trial, participants on 2.4 mg weekly lost around 15% of body weight on average over 68 weeks, against about 2.4% on placebo, with diet and activity support throughout.
  • Effects build slowly. The escalation schedule spans roughly four months before the maintenance dose is reached.
  • Averages are not individuals. Trial results include people who lost far more and people who lost very little.
  • Weight regain after stopping is well documented in follow-up studies. These were tested as ongoing treatments, not as a course.

Storage and handling

Freeze-dried powder
Refrigerated at 2–8 °C and protected from light. Stable for far longer than the reconstituted form.
After mixing
Refrigerated at 2–8 °C. Do not freeze. Discard if the solution is cloudy or has visible particles.
Long-term, frozen
Unopened lyophilised powder is stable at −20 °C or colder.

Printable one-pagerHow to reconstitute a vial, step by step

With other peptides

  • Tirzepatideincompatible

    Both act on the GLP-1 receptor. Combining them stacks the same mechanism rather than adding a new one, and compounds the gastrointestinal effects.

  • Retatrutideincompatible

    Overlapping GLP-1 agonism. These are alternatives to one another, not a stack.

  • Liraglutideincompatible

    Both are GLP-1 receptor agonists. Taking them together doubles the gastrointestinal effects and the pancreatitis risk while adding nothing. The receptor is already saturated at therapeutic doses of either.

  • Cagrilintidesynergistic

    The pairing under active development as CagriSema. Amylin and GLP-1 signal satiety through different receptors, so the effects add rather than overlap. The trial evidence is for a single manufactured combination product, not for mixing two separately sourced vials.

  • Orforglipronincompatible

    Both activate the GLP-1 receptor. Taking them together doubles the gastrointestinal effects and the pancreatitis risk while adding nothing — the receptor is already saturated at therapeutic doses of either.

  • Mazdutideincompatible

    Both fully activate the GLP-1 receptor. Running them together stacks one mechanism and its side effects rather than adding anything.

  • Survodutideincompatible

    Overlapping GLP-1 agonism. Running them together stacks one mechanism and its side effects.

  • Amylin and GLP-1 signal satiety through different receptors, which is the basis of the CagriSema combination. No trial has tested this pairing, and stacking two strong appetite suppressants risks intake falling below what is safe.

Check this against a whole stack

In use

Stacks with Semaglutide in them

Documented combinations, with full schedules.

Checking your vial

Research chemicals carry no manufacturing standard, so what the vial looks like is often the only quality signal available before you use it. More on assessing quality and COAs.

  • White cake, clear solution

    Correctly lyophilised powder forms a white cake and mixes to a completely clear solution.

  • Collapsed or melted cake

    Indicates heat exposure in transit.

  • Cloudiness or particles after mixing

    Do not use. This is also the standard instruction for the approved product.

Questions

How long does semaglutide take to leave the body?
Its half-life is around a week, so roughly five weeks pass before it is substantially cleared. This is why trials escalate the dose slowly and why a missed week does not produce an immediate drop-off.
Why do trial protocols increase the dose so gradually?
Gastrointestinal side effects, nausea above all, are strongly dose-related and worst when a dose first increases. Trial protocols raise the dose in steps over months specifically to limit that.
Does it need to be taken on the same day each week?
Trial protocols specified a fixed weekly day. With a half-life of about seven days, moving the day by a small amount changes blood levels very little, but a fixed schedule is easier to keep track of and is what was studied.

References

  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

    New England Journal of Medicine, 2021 · Randomised, double-blind, placebo-controlled phase 3 trial

    Adults with overweight or obesity, without diabetes · n = 1961 · 2.4 mg once weekly, after 16 weeks of escalation · 68 weeks

    Mean weight change of −14.9% with semaglutide against −2.4% with placebo. Gastrointestinal effects were the most common adverse events and were mostly transient.

    10.1056/NEJMoa2032183

Keep this page honest

If something here is wrong, out of date, or missing a source, tell us and we will fix it and say that we did.

Suggest a correction

This page is educational. It describes what published research reports, not what you should do. Peptides discussed here are largely not approved for human use, and nothing on Bioalmanac is medical advice. No clinician reviews these pages.

Page last updated 12 Aug 2026