What is semaglutide?
Semaglutide belongs to a drug class called GLP-1 receptor agonists. GLP-1, short for glucagon-like peptide-1, is a hormone the gut releases after eating. Natural GLP-1 is broken down within minutes. Semaglutide, made by the Danish company Novo Nordisk, was designed to last much longer: small changes to its sequence protect it from the enzyme that breaks GLP-1 down, and a fatty acid side chain lets it bind to albumin, a blood protein.
Semaglutide is an approved prescription medicine, not an experimental peptide. In the US it was approved in 2017 as Ozempic, an injection for type 2 diabetes, and in 2019 as Rybelsus, a tablet for type 2 diabetes. In 2021 it was approved as Wegovy for long-term weight management in adults with obesity, or with overweight and a related health condition, alongside diet and physical activity.
How does semaglutide work?
Semaglutide activates the GLP-1 receptor, the same target as the natural hormone. In the pancreas, this helps release insulin when blood sugar is high and lowers glucagon, a hormone that raises blood sugar. Because this depends on glucose levels, the drug on its own carries a low risk of very low blood sugar. It also slows how fast the stomach empties, so food stays there longer after a meal.
GLP-1 receptors are also found in brain areas that control hunger and fullness, which may explain why trial participants reported feeling less hungry and eating less. How it affects the heart and kidneys is still being studied, and may involve both weight and blood sugar changes and direct effects on blood vessels and inflammation.
What has research looked at?
- Type 2 diabetes
- The SUSTAIN (injection) and PIONEER (tablet) trial programs studied people with type 2 diabetes. Participants had lower HbA1c, a measure of average blood sugar, than with placebo and, in many trials, than with other diabetes drugs.
- Body weight
- The STEP trials studied adults with obesity or overweight who also received diet and activity advice. On average, participants on semaglutide lost substantially more weight than those on placebo, though results varied widely between people.
- Heart disease
- In the SELECT trial, adults with heart disease and overweight or obesity, but no diabetes, had fewer heart attacks, strokes and cardiovascular deaths combined than those on placebo. SUSTAIN-6 reported a similar finding in type 2 diabetes.
- Kidneys
- The FLOW trial studied people with type 2 diabetes and chronic kidney disease. Participants on semaglutide had a lower rate of serious kidney outcomes, such as major loss of kidney function, than those on placebo.
- Liver
- Trials in MASH, a more serious, inflammatory form of fatty liver disease, reported liver inflammation resolving in more participants on semaglutide than on placebo.
- Brain
- Two large trials of the tablet form in early Alzheimer's disease did not show that it slowed the disease.
Semaglutide has one of the largest evidence bases of any metabolic drug. The trials also show its limits. Results vary from person to person, part of the weight lost is muscle and other lean tissue, and in a follow-up of one large weight trial, participants regained much of the weight within a year of stopping.
Side effects and cautions
The most common side effects in trials were digestive: nausea, vomiting, diarrhea, constipation and stomach pain. They were most frequent early in treatment and often eased, but some participants stopped because of them. Severe vomiting or diarrhea can cause dehydration, which has been linked to sudden kidney injury. Headache, tiredness, dizziness and a faster resting heart rate were also reported, and serious allergic reactions are rare. A much smaller appetite can also make it harder to eat enough protein and nutrients. Anyone with health questions should talk to a qualified clinician.
- Pancreas and gallbladder
- Pancreatitis and gallbladder problems, including gallstones, have been reported and are known risks for this drug class.
- Thyroid
- Its US label carries a boxed warning because semaglutide caused thyroid C-cell tumors in rodents. It is not known whether this happens in people, but it is not used in people with a personal or family history of medullary thyroid cancer or MEN 2 syndrome.
- Low blood sugar
- The risk rises when it is combined with insulin or sulfonylurea diabetes drugs.
- Eyes
- In one type 2 diabetes trial, it was linked to more complications of diabetic eye disease, which can worsen for a time when blood sugar improves quickly. Studies have also linked it to a small increase in the risk of NAION, a rare optic nerve condition that can cause sudden vision loss, and European regulators concluded it is a very rare side effect.
- Surgery and pregnancy
- Because it slows stomach emptying, rare cases of stomach contents entering the lungs during general anesthesia or deep sedation have been reported. It is not recommended during pregnancy.
- Product content
- Health agencies have warned about counterfeit semaglutide products, which may not contain what their labels say.
Further reading
This page summarizes the research in plain words. To read the studies yourself:
- Published studies on Semaglutide PubMed, US National Library of Medicine
- Registered human trials of Semaglutide ClinicalTrials.gov
