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Lexicon
Weight management

Semaglutide

The most established member of the GLP-1 class: a single agonist with the broadest data base of the group.

5 min read 14 sources

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Compound approved · since 2017Lab tested in the shop

No time to read it all? The video sums up the whole entry in about a minute, from how it works to the studies and storage.

Summary

At a glance

Sources checked on 26 Oct 2026

Body weight in phase 3
-14.9 %

STEP 1 at 68 weeks, target dose of the obesity trials (placebo -2.4%)1

Cardiovascular events (SELECT)
-20 %

17,604 people with cardiovascular disease and overweight without diabetes, risk 0.80-fold2

Major kidney events (FLOW)
-24 %

3,533 people with type 2 diabetes and chronic kidney disease, median 3.4 years8

Half-life
~1 week

according to the label, more than 99 percent bound to albumin, fits one dose per week12

  • Semaglutide is a GLP-1 agonist: a modified GLP-1 with an attached fatty acid that is 94 percent identical to the body's own hormone and is injected once a week.1214
  • In phase 3 (STEP 1, 68 weeks) body weight fell by 14.9 percent on average, by 2.4 percent on placebo. In the study on eating, participants ate 35 percent less at a free meal.16
  • In large outcome trials there were 20 percent fewer cardiovascular events (SELECT) and 24 percent fewer major kidney events (FLOW). In fatty liver with inflammation, MASH resolved more often.289
  • The most common effects were gastrointestinal, mostly transient and mild to moderate. In type 2 diabetes complications of the retina occurred more often (SUSTAIN-6).13
  • According to ChEMBL Semaglutide has been approved since 2017. Everything here describes the state of research, not a recommendation.14
Profile

Updated May 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~7 days

Half-life ~7 days
After 14 days: 25 %
Day 7 · 50 %Day 14 · 25 %Day 21 · 12.5 %Day 35 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon.

Class
GLP-1 agonist

single

Frequency
Once weekly

subcutaneous

Half-life
~7 days
Form
Lyophilised powder

reconstituted with BAC water

Sizes
5 to 50 mg

6 sizes in the shop

Contents 16 sections
  1. At a glance
  2. What is Semaglutide?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Injection
  7. Dosing
  8. What the research shows
  9. Research status
  10. Side effects
  11. Lifestyle
  12. Storage
  13. Related compounds
  14. FAQ
  15. Glossary
  16. Sources

What is Semaglutide?

Semaglutide is the most established member of the GLP-1 class and, for many, the entry point into incretin research. Unlike Tirzepatide or Retatrutide it acts on just one receptor, the GLP-1 receptor. In return it is the longest- and most broadly studied molecule of the group.

It is injected once a week. The long half-life of about seven days makes that possible, the highest figure among the compounds listed here. Semaglutide ships as a freeze-dried powder you dissolve in bacteriostatic water before the first use.

Comparison

One, two or three receptors

Which receptors each compound targets, as stated in the TPD lexicon. Tap a card to open its entry.

Mono agonist Semaglutide GLP-1 GIP Glucagon 1 of 3 receptors
Dual agonist Tirzepatide GLP-1 GIP Glucagon 2 of 3 receptors Dual agonist Survodutide GLP-1 GIP Glucagon 2 of 3 receptors Triple agonist Retatrutide GLP-1 GIP Glucagon 3 of 3 receptors

Simplified: more receptors does not automatically mean better, each path also brings its own effects. 14

How it works

Semaglutide mimics the body's own GLP-1 hormone. It boosts the glucose-dependent insulin response, slows gastric emptying and engages the satiety centres in the brain. Day to day, most people mainly notice that appetite drops and the constant circling around food, the food noise, gets much quieter.

Because only one receptor is engaged, the per-milligram effect is milder than with the dual and triple agonists. In return the profile is very well understood and easy to steer.

Mechanism
  • GLP-1 Insulin response boosted · Gastric emptying slowed · More satiety in the brain
Through the GLP-1 receptor, Semaglutide boosts the glucose-dependent insulin response, slows gastric emptying and increases satiety in the brain. Simplified diagram.

Where it acts

One receptor, several organs

Tap a point or a card. Colour = receptor, grey = effect seen in trials.

  1. Brain

    Less hunger, more fullness, 35 percent less eaten at a free meal6

    GLP-1
  2. Pancreas

    HbA1c clearly lower than on placebo in type 2 diabetes5

    GLP-1
  3. Stomach

    After 20 weeks no sign of delayed gastric emptying in an indirect measurement6

    Observed in trials
  4. Heart and vessels

    Fewer cardiovascular events in overweight without diabetes2

    Observed in trials
  5. Kidney

    Fewer major kidney events in type 2 diabetes with kidney disease8

    Observed in trials
  6. Liver

    MASH resolved more often in phase 39

    Observed in trials
  7. Eye

    More retinal complications than on placebo in type 2 diabetes3

    Observed in trials

Targets in the ChEMBL database14

Compound CHEMBL2108724: one recorded mechanism, agonist with direct binding to the human receptor.

GLP-1 receptor
Gene
GLP1R
UniProt
P43220
ChEMBL
CHEMBL1784
Action
Agonist, direct binding
Large translucent blue cell with Y-shaped receptors that blue 3D peptide chains dock onto, a glowing glass dome in the background
Symbolic image.

What you need

Before you start, have everything ready. The list is short:

Supplies

5 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

Semaglutide vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid

  1. Semaglutide vial

    The Semaglutide vial with the freeze-dried powder

    In the shop

  2. Bacteriostatic water

    Bacteriostatic water to dissolve it

    In the shop

  3. U-100 insulin syringes

    U-100 insulin syringes for the injection (they also work for drawing the water, you just draw more often; a larger syringe is faster but not a must)

    Amazon (opens a new tab)

  4. Alcohol swabs

    Alcohol swabs for the vial cap and the skin

    Amazon (opens a new tab)

  5. Sharps container

    A sealable sharps container for used needles

As an Amazon associate we earn from qualifying purchases. Links open Amazon - no extra cost for you.

With everything clean and in one place, the rest is straightforward.

Reconstitution

The powder is dissolved in bacteriostatic water. How much water you add sets the concentration and therefore how many units you later draw on the insulin syringe for your dose.

Use the peptide calculator for exactly this: pick your vial size and the water volume to instantly see the concentration and the units per dose. Roughly: less water means higher concentration and fewer units. For large vials from 20mg up, more water is worth it, otherwise the dose gets tiny and hard to read.

When dissolving, just add the bac water and let the powder dissolve. It does not matter if the water hits the powder directly. Swirling or shaking are both fine.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Injection

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front and the inner side of the thigh, or the back of the upper arm.

The short version:

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts
Semaglutide vial on a white shelf with an insulin syringe and a closed light blue notebook
Symbolic image.

What the research shows

Semaglutide has the largest data base of the whole class. In obesity research (the STEP programme), weekly dosing over a good year led to roughly 15 percent weight reduction on average. In diabetes and cardiovascular studies (SUSTAIN, SELECT), alongside the blood-sugar and weight effect, benefits on cardiovascular endpoints showed up too.

The individual studies with links are in the source block below.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Body weight at the end of the trial1119

Mean change in percent per trial

STEP 11 Overweight without diabetes, 68 weeks
Placebo -2.4%
Target dose of the obesity trials -14.9%
STEP UP11 Obesity without diabetes, 72 weeks, phase 3b
Placebo -3.9%
Target dose of the obesity trials -15.6%
Higher dose (STEP UP) -18.7%
ESSENCE9 Fatty liver with inflammation and fibrosis, 72 weeks
Placebo -2.0%
Target dose of the obesity trials -10.5%

Values as stated in the abstracts, for all participants regardless of discontinuation or rescue treatment. The higher dose from STEP UP gave 3.1 percentage points more on average, but also more side effects (see tolerability). The trials are not directly comparable.

Body weight from week 207

Mean change from week 20 in percent, STEP 4 with 803 randomised participants

0-5%-10% Week 20Week 68 +6.9%-7.9%

Semaglutide continued: Week 20 0.0%, Week 68 -7.9%. Placebo from week 20: Week 20 0.0%, Week 68 +6.9%.

Everyone first received Semaglutide for 20 weeks and lost 10.6 percent on average. Then participants were randomised: continue Semaglutide or switch to placebo. By week 68 the continued group lost a further 7.9 percent, the placebo group regained 6.9 percent. Only the time points from the abstract are shown.

Major cardiovascular events23

Share of participants with cardiovascular death, heart attack or stroke

SELECT2 Cardiovascular disease and overweight without diabetes, mean 39.8 months
Placebo 8.0%
Target dose of the obesity trials 6.5%
SUSTAIN-63 Type 2 diabetes at high risk, 104 weeks
Placebo 8.9%
Semaglutide (both doses combined) 6.6%

Values from the abstracts. In SELECT the risk was 0.80, in SUSTAIN-6 0.74 compared with placebo. In SUSTAIN-6 complications of the retina occurred more often (risk 1.76).

Liver biopsy after 72 weeks9

Share of participants, interim analysis of ESSENCE with 800 participants

MASH resolved9 Without worsening of fibrosis
Placebo 34.3%
Target dose of the obesity trials 62.9%
Fibrosis improved9 Without worsening of MASH
Placebo 22.4%
Target dose of the obesity trials 36.8%
Both together9
Placebo 16.1%
Target dose of the obesity trials 32.7%

Participants with biopsy-confirmed MASH and fibrosis stage 2 or 3. The trial runs for 240 weeks in total, this is the planned interim analysis.

Long-term blood sugar HbA1c at 30 weeks5

Change in percentage points, SUSTAIN 1, mean baseline 8.05 percent

SUSTAIN 15 Type 2 diabetes without other drugs
Placebo -0.02 pp
Lower dose (SUSTAIN) -1.45 pp
Higher dose (SUSTAIN) -1.55 pp

Values as stated in the abstract. Body weight fell by 3.73 and 4.53 kg in the two groups, by 0.98 kg on placebo.

Glass blood vessel with a reddish inner ring and a glass heart model on a bright lab table
Symbolic image.

Research status

Where the research stands

Semaglutide is one of the most studied compounds: the registry lists about 790 records, including those with Semaglutide only as a comparator. Here is a selection of the developer's trials with the injection whose results are cited on this page, plus early phase 1 studies. As of 26 Oct 2026. 13

  1. Preclinical Modified GLP-1 with a fatty acid
  2. Phase 1 5 trials, 5 completed
  3. Phase 2 2 trials, 2 completed
  4. Phase 3 8 trials, 7 completed
  5. Approval since 2017
30,297 participants in phase 3 Approved. ChEMBL lists Semaglutide with phase 4 as the highest phase and a first approval in 2017.14
Show all 10 phase 2 and 3 trials on a timelineHide timeline 9 completed 1 running 10 with results
Phase 2
Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026. Phase 1: 5 trials on safety and pharmacokinetics, not shown as bars.

Side effects

The most common effects are gastrointestinal: nausea, fullness, sometimes diarrhoea or constipation. They show up mainly at the start and after each dose increase. They usually ease once the body has adjusted. That is exactly what the slow titration is for. Going up too fast is the most common avoidable mistake.

In a few participants with type 2 diabetes a large trial saw complications of the retina, slightly more often than with placebo (SUSTAIN-6).

Tolerability

Frequency in the trials

Out of 100 participants per group, how many had the event. STEP UP over 72 weeks, SUSTAIN 1 over 30 weeks.

43 of 100 Placebo
61 of 100 Target dose of the obesity trials
71 of 100 Higher dose (STEP UP)
Event PlaceboTarget dose of the obesity trialsHigher dose (STEP UP)
Gastrointestinal effects, STEP UP11 43%61%71%
Altered skin sensation, STEP UP11 1%6%23%
Nausea, SUSTAIN 15 8%0%0%
Diarrhoea, SUSTAIN 15 2%0%0%

Values from the abstracts, SUSTAIN 1 rounded. The complaints were mostly transient and mild to moderate. In STEP 1 4.5 percent stopped because of gastrointestinal effects, 0.8 percent on placebo. In SELECT 16.6 percent stopped treatment because of side effects, 8.2 percent on placebo.11512

Lifestyle

Semaglutide takes the hunger away, the rest is on you. A few things get more out of the research phase and keep you healthy:

  1. Enough protein

    If you eat little, make the little you eat protein-rich, or you lose muscle along with fat.

  2. Drink enough

    With low appetite you often drink less without noticing. The risk of dehydration then goes up.

  3. Resistance training

    Keeps muscle mass while the weight comes off.

  4. Eat slowly

    With delayed gastric emptying you fill up faster, big portions sit heavy.

Plate with grilled chicken, broccoli and carrots, next to a glass of water and a light blue napkin on a bright table

Alcohol and very fatty meals make the nausea noticeably worse, especially early on.

Storage

The undissolved powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. Once dissolved, the solution goes into the fridge (2 to 8 degrees) and stays stable there for at least 4 to 6 months with barely any loss of potency, in practice considerably longer. The bacteriostatic water brings a preservative that keeps the dissolved form stable for longer.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed.

Dissolved (mixed) Fridge, 2 to 8 degrees

At least 4 to 6 months with barely any loss of potency. The bacteriostatic water brings a preservative.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.
Level · Semaglutide

How the level builds up

One dose per week: each dose adds to what is left of the previous one.

Lexicon: Once weekly (subcutaneous)
Peak 2×Trough 1×
Day 28 · 5. dose
1.94× of the first dose
Plateau
from Day 28

97 % of the plateau after dose 5

Peak
2×

of the first dose

Trough
1×

before the next dose

Simplified model, values relative to the first dose, no dosing information. Dashed: the first dose alone, green: the plateau.

Related

Related compounds

Same receptors, blends with Semaglutide or a different path: all in the TPD lexicon.

Semaglutide
Semaglutide Oral Same compound, as a tablet CagriSema (Cagri + Sema) Semaglutide plus cagrilintide Tirzepatide GLP-1 and GIP Retatrutide Triple agonist Survodutide GLP-1 and glucagon Mazdutide GLP-1 and glucagon Orforglipron GLP-1, as a tablet Cagrilintide Different path: amylin

FAQ

Common questions about Semaglutide

Short answers, each backed by the sources below.

Is Semaglutide approved?

Yes. ChEMBL lists Semaglutide with phase 4 as the highest phase and a first approval in 2017. As an injection it is given once a week, there is also a tablet (separate entry). The information here describes the state of research and is not a recommendation for use.1412

How does Semaglutide differ from Tirzepatide and Retatrutide?

The number of receptors. Semaglutide acts only on the GLP-1 receptor, Tirzepatide also on GIP, Retatrutide additionally on the glucagon receptor. In return Semaglutide has the longest series of trials in the group, with large outcome trials on heart, kidney and liver.14289

What did the weight trials show?

In STEP 1 weight fell by 14.9 percent on average after 68 weeks, by 2.4 percent on placebo. Half of the participants lost at least 15 percent. In STEP 4 those who switched to placebo after 20 weeks regained weight: 6.9 percent by week 68, while the other group lost a further 7.9 percent.17

What is known about heart, kidney and liver?

In SELECT (cardiovascular disease, overweight without diabetes) there were 6.5 versus 8.0 percent major cardiovascular events. In FLOW (type 2 diabetes with kidney disease) the risk of major kidney events was 24 percent lower. In ESSENCE MASH resolved after 72 weeks in 62.9 percent, in 34.3 percent on placebo.289

How high were the doses in trials?

The highest study dose was 16 mg per week in a phase 2 trial in type 2 diabetes. Compared with the lowest dose there, blood sugar fell barely more, weight somewhat more, but there were more side effects and discontinuations. In STEP UP a higher dose also brought more weight loss and more complaints. The entry describes the opposite as a principle: start low and only increase until an effect is noticeable. This is not a dosing recommendation.1011

Which side effects were seen?

Most often nausea and diarrhoea, mostly transient and mild to moderate. In STEP 1 4.5 percent stopped because of gastrointestinal effects, 0.8 percent on placebo. In SUSTAIN-6 complications of the retina occurred more often in type 2 diabetes. With the higher dose from STEP UP altered skin sensations were more common.1311

How long does Semaglutide stay in the body?

According to the label the half-life is about one week, Semaglutide is still in the blood for about five weeks after the last dose. More than 99 percent is bound to the blood protein albumin. A steady level is reached after four to five weeks of weekly dosing.12

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Agonist
A substance that binds to a receptor and activates it, like the body's own messenger.
Albumin
The most common protein in the blood. Semaglutide binds to it through an attached fatty acid and is broken down more slowly.
Food noise
Colloquial term for constantly thinking about food. In studies measured as hunger, cravings and control over eating.
GLP-1
Glucagon-like peptide 1: gut hormone that releases insulin, slows gastric emptying and signals fullness in the brain.
Half-life
Time after which only half of a substance is left in the blood. At about one week one dose per week is enough.
HbA1c
Long-term blood sugar: reflects average blood sugar over the past eight to twelve weeks.
Incretins
Gut hormones such as GLP-1 and GIP that are released after eating and boost the insulin response.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
MASH
Metabolic dysfunction-associated steatohepatitis, fatty liver with inflammation, formerly mostly called NASH. It can lead to scarring (fibrosis).
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Receptor
Protein on the cell surface that a messenger docks onto. Only then does the cell respond.
Subcutaneous
Into the fat layer just under the skin.

Evidence

Sources

Show all 14 sourcesHide sources 11 Studies1 Trial registry2 Database checked 26 Oct 2026

Studies

  1. Phase 3 trial STEP 1 in overweight

    Wilding et al., New England Journal of Medicine, 2021

    DOI 10.1056/NEJMoa2032183 PMID 33567185 NCT03548935
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Phase 3 trial SELECT on cardiovascular events without diabetes

    Lincoff et al., New England Journal of Medicine, 2023

    DOI 10.1056/NEJMoa2307563 PMID 37952131 NCT03574597
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Phase 3 trial SUSTAIN-6 on cardiovascular events in type 2 diabetes

    Marso et al., New England Journal of Medicine, 2016

    DOI 10.1056/NEJMoa1607141 PMID 27633186 NCT01720446
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Phase 2 dose-finding trial in type 2 diabetes

    Nauck et al., Diabetes Care, 2016

    DOI 10.2337/dc15-0165 PMID 26358288 NCT00696657
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Phase 3 trial SUSTAIN 1 in type 2 diabetes

    Sorli et al., The Lancet Diabetes & Endocrinology, 2017

    DOI 10.1016/S2213-8587(17)30013-X PMID 28110911 NCT02054897
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. Study on appetite, food intake and gastric emptying

    Friedrichsen et al., Diabetes, Obesity and Metabolism, 2021

    DOI 10.1111/dom.14280 PMID 33269530
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. Phase 3 trial STEP 4 on continuing or stopping

    Rubino et al., JAMA, 2021

    DOI 10.1001/jama.2021.3224 PMID 33755728 NCT03548987
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  8. Phase 3 trial FLOW on kidney disease in type 2 diabetes

    Perkovic et al., New England Journal of Medicine, 2024

    DOI 10.1056/NEJMoa2403347 PMID 38785209 NCT03819153
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  9. Phase 3 trial ESSENCE in MASH, interim analysis

    Sanyal et al., New England Journal of Medicine, 2025

    DOI 10.1056/NEJMoa2413258 PMID 40305708 NCT04822181
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  10. Phase 2 trial with higher investigational doses in type 2 diabetes

    Aroda et al., Diabetes Care, 2025

    DOI 10.2337/dc24-2425 PMID 40279144 NCT05486065
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  11. Phase 3b trial STEP UP with a higher dose

    Wharton et al., The Lancet Diabetes & Endocrinology, 2025

    DOI 10.1016/S2213-8587(25)00226-8 PMID 40961952 NCT05646706
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. All trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US prescribing information for the semaglutide injection

    DailyMed, U.S. National Library of Medicine (Stand 10.06.2026)

    Checked 26 Oct 2026 via DailyMed
  2. Mechanism, target and approval status in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL2108724)

    Checked 26 Oct 2026 via ChEMBL

In the shop

Semaglutide in the catalog

Sizes, prices and shipping times are on the product page.

To the product