Semaglutide: what the research shows
A copy of a gut hormone that makes you feel full. One of the most studied weight-loss medicines in the world.
Also known as Ozempic, Wegovy, Rybelsus
At a glance
14.9%
average weight lost in 68 weeks
STEP 1 trial, 1,961 adults · placebo: 2.4%
Approved in the US, EU and many other countries. Ozempic and Rybelsus treat type 2 diabetes; Wegovy is for weight management. A daily Wegovy pill was approved in the US in December 2025.
Step 1 of 5: Cells
Step 2 of 5: Animals
Step 3 of 5: Small human studies
Step 4 of 5: Large trials
Step 5 of 5: Approved medicine
What is Semaglutide?
Semaglutide is a man-made version of GLP-1, a hormone your gut releases after you eat. The natural hormone is broken down within minutes. Semaglutide was changed slightly so it lasts about a week, which is why the injection is given once a week.
How does Semaglutide work?
GLP-1 tells your brain you’re full, slows down how fast your stomach empties, and helps your body release insulin when blood sugar rises. Semaglutide does the same, for much longer.
What does the research show?
STEP 1 trial · 1,961 adults with obesity or overweight, compared with a placebo (a dummy injection)
Semaglutide
Placebo
Source: Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) · Wilding et al. · New England Journal of Medicine · 2021
SELECT trial · 17,604 adults with heart disease and overweight
Semaglutide
Placebo
A 20% lower risk of these events than on placebo.
Source: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) · Lincoff et al. · New England Journal of Medicine · 2023
OASIS 4 trial · 307 adults with obesity or overweight
Semaglutide pill
Placebo
Source: Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4) · Wharton et al. · New England Journal of Medicine · 2025
- In the STEP 1 trial, 1,961 adults with obesity took weekly semaglutide for 68 weeks. They lost 14.9% of their body weight on average, compared with 2.4% on a placebo (a dummy injection).
- About half of the people on semaglutide lost 15% or more of their body weight. On placebo, fewer than 1 in 20 did.
- In the SELECT trial of 17,604 people with heart disease and overweight, semaglutide lowered the risk of a heart attack, stroke or heart-related death by 20%. Over about three years, 6.5% had one of these events, compared with 8.0% on placebo.
- A once-a-day pill version led to 13.6% weight loss over 64 weeks in the OASIS 4 trial, compared with 2.2% on placebo.
How do the weight-loss results compare?
Each medicine compared with a placebo in its own trial. Ordered by reported average; this is not a head-to-head ranking.
- Medicine
- Placebo
Retatrutide · Experimental
12 mg weekly
Phase 2 · 48 weeks · 338 people
Tirzepatide · Approved
15 mg weekly (Zepbound)
SURMOUNT-1 · 72 weeks · 2,539 people
Semaglutide · Approved
2.4 mg weekly injection (Wegovy)
STEP 1 · 68 weeks · 1,961 people
Semaglutide · Approved (US)
25 mg daily pill (Wegovy pill)
OASIS 4 · 64 weeks · 307 people
Average body weight lost
Each human trial had different people, doses and lengths, so compare with care. The bars describe approved or experimental medicines studied under medical supervision with diet and exercise advice, not laboratory research products. They use full journal reports; conference findings and different endpoints appear separately below.
Show these numbers as a table
| Medicine | Trial | People | Weeks | Medicine | Placebo | Source |
|---|---|---|---|---|---|---|
| Retatrutide, 12 mg weekly | Phase 2 | 338 | 48 | 24.2% | 2.1% | PubMed |
| Tirzepatide, 15 mg weekly (Zepbound) | SURMOUNT-1 | 2,539 | 72 | 20.9% | 3.1% | PubMed |
| Semaglutide, 2.4 mg weekly injection (Wegovy) | STEP 1 | 1,961 | 68 | 14.9% | 2.4% | PubMed |
| Semaglutide, 25 mg daily pill (Wegovy pill) | OASIS 4 | 307 | 64 | 13.6% | 2.2% | PubMed |
PTT-A and CBL-514: evidence so far
Neither has a comparable average human body-weight-loss result in the research below. Animal body weight and human fat volume measure different things, so they are shown separately from the bars.
Animal research · conference abstract
PTT-A
- Average human body-weight loss
- Not established in the cited research
- What was measured
- Body weight in diet-induced obese rats over 21 days
- Reported finding
- Body weight was 19.2% lower versus vehicle at the higher studied exposure; tirzepatide was 12.1% lower versus vehicle in the same experiment.
A difference versus vehicle in rats is not average weight lost by people. It cannot establish superiority to retatrutide in humans.
Human fat-volume subgroup · conference report
CBL-514
- Average human body-weight loss
- Not established by this fat-volume result
- What was measured
- MRI-measured visceral-fat volume, four weeks after final treatment
- Reported finding
- Visceral-fat volume fell 12.01%; placebo rose 5.68%. The small phase 2 subgroup had 40 participants with later follow-up data.
12.01% less visceral fat is not 12.01% less body weight. CBL-514 is an experimental small molecule, not a peptide.
What we don't know yet
- Why some people lose a lot of weight on it and others very little.
- How to keep the weight off after stopping: most people regain much of it.
- Effects over decades. The largest trials followed people for a few years.
Known risks and side effects
- Stomach side effects are common: nausea, diarrhea, vomiting and constipation, especially while the dose is being raised.
- Less common but serious problems include inflammation of the pancreas (pancreatitis) and gallbladder problems.
- In the US the label warns about a type of thyroid tumor seen in rodents, so people with a family history of medullary thyroid cancer are told not to use it.
- Weight usually comes back after the medicine is stopped.
Is Semaglutide approved?
A medicines regulator, such as the FDA in the US or the EMA in Europe, has approved it for specific uses.
Approved in the US, EU and many other countries. Ozempic and Rybelsus treat type 2 diabetes; Wegovy is for weight management. A daily Wegovy pill was approved in the US in December 2025.
From the community
Watch: Semaglutide and related science
Start with the compound discussion, then use the background lesson to understand its biology. Each card explains its connection. Recordings may predate later findings or regulatory changes.
Ohio State Wexner Medical Center
Ozempic, Mounjaro, Wegovy and Zepbound: which is which?
How the brand names relate to semaglutide and tirzepatide and their prescribed uses. Older recordings may not cover later indications or formulations.
Allison L. Rhodes, MD · obesity medicine
Discusses the compound
Discusses Semaglutide or its clinical context. Read the original studies linked here for the exact formulation, population and outcomes.
Nick Norwitz
The science behind Ozempic and other GLP-1 medications
How GLP-1 medicines work in the gut and brain, in clear language.
Nick Norwitz, MD, PhD
Discusses the compound
Discusses Semaglutide or its clinical context. Read the original studies linked here for the exact formulation, population and outcomes.
Ohio State Wexner Medical Center
What is a GLP-1 agonist, and how does it work?
A hospital explainer of GLP-1 signalling, appetite and blood-sugar regulation.
Allison L. Rhodes, MD · obesity medicine
Related biology
Background on GLP-1 signalling for understanding Semaglutide. It does not demonstrate benefits of this compound or formulation.
Sources and references
- Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)Wilding et al. · New England Journal of Medicine · 2021
- Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)Lincoff et al. · New England Journal of Medicine · 2023
- Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4)Wharton et al. · New England Journal of Medicine · 2025
- Discovery of the Once-Weekly GLP-1 Analogue SemaglutideLau et al. · Journal of Medicinal Chemistry · 2015
VETUD Learn explains published research in plain language. It is general information, not medical advice. Talk to a doctor before starting, stopping or changing any treatment.
In the research shop
Check the catalog for related laboratory research materials. These products are separate from the approved medicines and clinical trial formulations discussed here.
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