Semaglutide
Semaglutide (GLP-1 Receptor Agonist)
Also called Ozempic, Wegovy, Rybelsus, semaglutida
The GLP-1 drug behind Ozempic and Wegovy
Semaglutide is a once-weekly injection sold as Ozempic for type 2 diabetes and Wegovy for weight loss, with a daily tablet version called Rybelsus. It copies a gut hormone that tells the brain you are full. It is an approved medicine, and its SELECT trial showed fewer heart attacks and strokes in people with heart disease and obesity.
A weekly injection sold as Ozempic for diabetes and Wegovy for weight loss. It is a rebuilt copy of a hormone your gut releases after eating, the one that tells your brain you are full, engineered to last a week instead of minutes. Its SELECT trial also showed fewer heart attacks and strokes in people with heart disease and obesity, which became an approved use for Wegovy.
- Half-life
- About a week
- Route studied
- Subcutaneous injection, or oral tablet (label)
- Status
- Prescription (Ozempic, Wegovy, Rybelsus)
Tested in several human trials
5,178 papers · 317 clinical trials
What Semaglutide has been studied for
The reasons people look it up, roughly in order of how often, and what research exists for each. Interest in a use is not evidence that it works; the evidence is stated under each one.
- Weight loss
- Approved as Wegovy for chronic weight management. In STEP 1, average loss was about 15% of body weight over 68 weeks, sustained to two years in STEP 5.
- Type 2 diabetes
- Its first approved use, sold as Ozempic.
- Heart attack and stroke risk
- An approved use for Wegovy, based on SELECT: a 20% reduction in serious cardiovascular events in people with heart disease and obesity but no diabetes.
- Kidney disease
- Tested in people with obesity and chronic kidney disease without diabetes.
Mechanism of Action
How Semaglutide works
There is a hormone your gut releases when you eat, called GLP-1, whose job is to tell your brain you have had enough. It works, and then it disappears within minutes. Semaglutide is that hormone rebuilt so it lasts about a week.
Three things happen at once
The first is appetite. It reaches the parts of the brain that set hunger, and the usual description from people taking it is not willpower but silence: the constant low-level negotiation about food stops.
The second is your stomach. It empties more slowly, so a meal keeps feeling like a meal for longer.
The third is insulin, and the detail here is genuinely clever. It only prompts insulin when blood sugar is actually raised. Older diabetes drugs pushed insulin regardless, which is how people ended up shaky and sweating between meals. This one responds to the situation instead.
The result that matters most
Weight loss is what it is famous for, at around 15% of body weight over 68 weeks. But the more important trial was not about weight at all. In 17,604 people with existing heart disease and obesity, it cut the rate of heart attacks, strokes and cardiovascular death from 8.0% to 6.5%.
That is the difference between a drug that changes a number on a scale and one shown to change outcomes. It is why Wegovy's label includes reducing the risk of major cardiovascular events in adults with heart disease and obesity.
The honest catch
Gut side effects are common, mostly while the dose is climbing, and they are the usual reason people stop. And as with tirzepatide, stopping brings the weight back.
Semaglutide side effects: what studies reported
Documented in large trials and years of prescribing. Mostly digestive, and in the STEP trials mostly during the dose escalation period.
Most commonly reported
- Nausea, the most common reason people stop
- Constipation
- Diarrhoea
- Reflux and burping
- Food losing its appeal, sometimes including things you used to love
- Feeling full very quickly
Worth keeping an eye on
- Muscle loss alongside fat
- Hair shedding around month three or four, usually a response to rapid weight loss rather than the drug
- Gallstones when weight comes off quickly
- Facial changes people call Ozempic face, which is fat loss rather than anything the drug does to skin
Reasons to call someone
- Severe, persistent stomach pain radiating to the back
- Vision changes, particularly if you have diabetic eye disease and your blood sugar has dropped fast
Dose-related findings. In the STEP trials, gastrointestinal effects were most frequent during the 16-week dose escalation set out in the Wegovy label.
Source: STEP and SUSTAIN trial programmes, plus years of prescribing data. This is a summary of published findings, not a complete safety profile and not medical advice. Questions about Semaglutide belong with a licensed clinician who knows your history.
Your Genetics & Semaglutide
The genes involved in how Semaglutide works
Semaglutide works through the receptors these genes build, and the genes vary from person to person. Researchers have linked some of that variation to differences in how people respond. A DNA report tells you which versions you carry.
GLP1R · ••
The Gly168Ser variant sits in the GLP-1 receptor semaglutide acts on. Some human cohort studies of GLP-1 drugs have associated it with differences in weight loss, and results have not been consistent. No study has shown that it should change how semaglutide is used.
TCF7L2 · ••
The common variant most strongly linked to type 2 diabetes risk; T-allele carriers tend to release less insulin after meals. It has been studied as a modifier of blood-sugar response to diabetes drugs, and is not established as one for semaglutide.
Beta-arrestin 1 is involved in pulling the GLP-1 receptor back inside the cell after it is activated. Studies of this variant with GLP-1 drugs are early, and any effect on semaglutide response is a hypothesis.
PCSK1 · ••
Proprotein convertase 1 processes proglucagon into the body's own GLP-1. Variants that reduce its activity are associated with obesity risk in population studies. Whether they change response to semaglutide has not been shown.
The dots after each gene are where your own result goes. Your report fills them in with the two letters you carry at that position.
Which of these variants do you carry?
Your report reads the DNA file you already have against this research.
Access
Access and legal status
Semaglutide: Prescription (Ozempic, Wegovy, Rybelsus). Decisions about any prescription medicine belong to a prescriber. We don't link to any seller, and nothing on this page is a recommendation to obtain or use it.
Your DNA and Semaglutide: see which of the variants studied alongside it you carry, and what that research does and does not show. Read my DNA, $99 →
Educational information only, not medical advice. Most peptides are not FDA-approved. Do not start, stop or change any medication or peptide because of this page; talk to a licensed clinician.
Worth knowing about Semaglutide
Interactions and situations where there is a specific reason to be careful. Where the honest answer is that nobody has studied something, it says so and says what that leaves open.
- Gut effects are common and are why most people stop
- Nausea, diarrhoea, constipation and vomiting are the most frequently reported problems, mostly mild to moderate and worst while the dose is being increased. In the two-year trial, 82% on semaglutide reported a gut side effect at some point, against 54% on placebo.
- Compounded semaglutide is not the trialled drug
- Every number here comes from the manufacturer's product. Compounded versions sold through telehealth have not been through these trials, and some use a different salt form that was never studied at all.
- Weight returns after stopping
- The trial that withdrew treatment saw weight regained. It is studied and labelled as an ongoing treatment rather than a course you finish.
The evidence behind Semaglutide
Along with tirzepatide, this is as good as evidence gets on this site: hundreds of randomised trials and an approved medicine rather than a research chemical. One trial below deserves singling out. SELECT enrolled 17,604 people and measured heart attacks and strokes rather than weight, which is the difference between a drug that changes a number and one shown to change what happens to you.
The literature, counted
Counted in PubMed on 3 August 2026 for semaglutide. Every figure links to the search that produced it, so you can re-run it. “Tagged human” is not the same as a human trial: that tag also covers work on human cells and reviews discussing people, which is why the trial count is given separately.
Studied in people
3 of 8The only kind that directly answers whether it works in humans.New England Journal of Medicine · 2023
HumanSemaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.
A trial that measured events rather than weight. Among 17,604 people with existing heart disease and obesity but no diabetes, cardiovascular death, heart attack or stroke occurred in 6.5% on semaglutide against 8.0% on placebo, a 20% reduction in risk.
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes: source for Semaglutide (opens in a new tab)Phase 3 · n=17,604 · mean 40 months
Read the paperNew England Journal of Medicine · 2021
HumanOnce-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding JPH, Batterham RL, Calanna S, et al.
The trial behind the weight-loss approval, known as STEP 1. Average loss was 15.3 kg against 2.6 kg on placebo. Half the semaglutide group lost at least 15% of their body weight, against 5% on placebo.
Once-Weekly Semaglutide in Adults with Overweight or Obesity: source for Semaglutide (opens in a new tab)Phase 3 · 68 weeks
Read the paperNature Medicine · 2022
HumanTwo-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial
Garvey WT, Batterham RL, Bhatta M, et al.
Answers the obvious question about whether it lasts. At two years the semaglutide group was 15.2% lighter against 2.6% on placebo, so the effect held rather than fading. It also reports the honest side of that: 82% had a gut side effect at some point.
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial: source for Semaglutide (opens in a new tab)Phase 3 · 104 weeks
Read the paper
Every source behind this page85 more
- Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical TrialRubino D, Abrahamsson N, Davies M, et al. · JAMA · 2021 · Phase 3Human
- Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical TrialRubino DM, Greenway FL, Khalid U, et al. · JAMA · 2022 · Phase 3Human
- Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trialKnop FK, Aroda VR, do Vale RD, et al. · Lancet · 2023 · Phase 3Human
- Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trialApperloo EM, Tuttle KR, Pavo I, et al. · Nature Medicine · 2025 · Phase 3Human
- Tirzepatide as Compared with Semaglutide for the Treatment of ObesityAronne LJ, Horn DB, le Roux CW, et al. · New England Journal of Medicine · 2025 · Phase 3bHuman
Everything we cite for Semaglutide, including preclinical work and early research. Each link goes to the source itself, so you can judge it rather than take our word for it.
Last updated · literature counts verified against PubMed on
Frequently Asked Questions
Is semaglutide affected by CYP enzyme genetics?
No. Unlike most drugs, semaglutide is not broken down by cytochrome P450 (CYP) enzymes. It is degraded by general protein-cutting enzymes after it comes off albumin, so CYP gene variants do not affect how it is cleared.
Do genes affect semaglutide response?
Research is early and mixed. Some cohort studies have associated GLP1R variants such as rs6923761 with differences in weight loss on GLP-1 drugs, and TCF7L2 rs7903146 with blood-sugar traits, but no variant is established as a predictor of response to semaglutide. These are receptor and pathway genes, not drug-clearance genes.
How much weight loss can semaglutide produce?
In STEP 1, adults on the Wegovy 2.4 mg weekly maintenance dose lost an average of about 15% of body weight over 68 weeks, against about 2.4% on placebo. Individual results varied widely: roughly 1 in 7 lost under 5%. Nobody can predict an individual result.
Watch
What clinicians and researchers say about Semaglutide
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Your DNA and Semaglutide
What the research says about your variants.
The report
Which Semaglutide variants do you carry?
Your report reads the DNA file you already have against the published research on 31 peptides, marker by marker, and says what that research does and does not show.
Read my DNA, $99