Semaglutide
Semaglutide is an anti-diabetic medication used for the treatment of type2 diabetes, and an anti-obesity medication used for long-term weight management and to reduce the risk of major adverse cardiovascular events. It is a peptide similar to the hormone glucagon-like peptide-1, modified with a side chain. It can be administered by subcutaneous injection or taken orally. It is sold by Novo Nordisk under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight management, weight loss, and the treatment of metabolic-associated steatohepatitis.
Semaglutide is a glucagon-like peptide-1 receptor agonist. The most common side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation.
It was approved for medical use in the US in 2017. In 2023, it was the nineteenth most commonly prescribed medication in the United States, with more than 25million prescriptions. It is on the World Health Organization's List of Essential Medicines.
Medical uses
United States
In the US, semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type2 diabetes, and to reduce the risk of major adverse cardiovascular events in adults with type2 diabetes and established cardiovascular disease.In combination with a reduced calorie diet and increased physical activity, semaglutide is also indicated in the US for reducing the risk of major adverse cardiovascular events in adults with established cardiovascular disease and who are either obese or overweight, for reducing excess body weight and maintaining weight reduction long term in obese individuals twelve years of age or older, and for overweight adults with at least one weight-related comorbid condition. After stopping semaglutide, individuals on average regain about two-thirds of the weight they lost during treatment within the following year.
In August 2025, the US Food and Drug Administration expanded the indication for semaglutide to include the treatment of metabolic-associated steatohepatitis in adults with moderate to advanced fibrosis.
In October 2025, the FDA further expanded the indication for semaglutide to reduce the risk of major adverse cardiovascular events in adults with type2 diabetes who are at high risk for these events.
In December 2025, the FDA approved an oral version of semaglutide sold under the brand name Wegovy for weight management.
European Union
In the European Union, semaglutide is indicated for the treatment of adults with insufficiently controlled type2 diabetes as an adjunct to diet and exercise as monotherapy when metformin is considered inappropriate due to intolerance or contraindications, in addition to other medicinal products for the treatment of diabetes.In the EU, semaglutide is further indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with obesity, hypertension, dyslipidemia, or cardiovascular disease. It is also indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adolescents with obesity and body weight above.
Side effects
Possible adverse effects include nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, indigestion/heartburn, dizziness, abdominal distension, belching, hypoglycemia in people with type2 diabetes, flatulence, gastroenteritis, and gastroesophageal reflux disease. It has in the past been suspected to cause pancreatitis, and can cause gastroparesis and bowel obstruction. Among people who were prescribed a glucagon-like peptide-1 medication, 0.1% were diagnosed with gastroparesis at least six months later, which equates to a 52% increased risk of being diagnosed with gastroparesis while on a GLP-1 medication. A 2019 meta-analysis did not indicate a significantly elevated risk of acute pancreatitis.The US prescription label for semaglutide contains a boxed warning for thyroid C-cell tumors in rodents. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans.
Contraindications
Semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or in people with multiple endocrine neoplasia type2.Mechanism of action
Semaglutide is a glucagon-like peptide-1 receptor agonist. The drug decreases blood sugar levels. The decrease is theorized to be caused by the mimicking of glucagon-like peptide-1, an incretin. It also appears to enhance growth of pancreatic beta cells, which are responsible for insulin production and release. Additionally, it inhibits the production of glucagon, the hormone that increases glycogenolysis and gluconeogenesis. It reduces food intake by lowering appetite and slowing down digestion in the stomach, helping reduce body weight.Structure and pharmacology
Semaglutide is chemically similar to human GLP-1. The first six amino acids of GLP-1 are missing. Substitutions are made at GLP positions 8 and 34, where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine, respectively. The substitution of the alanine prevents chemical breakdown by dipeptidyl peptidase-4. The lysine at GLP position 26 has a long chain attached, ending with a chain of 18 carbon atoms and a carboxyl group. This increases the drug's binding to blood protein, which enables longer presence in the blood circulation.Semaglutide's half-life in the blood is about seven days.
History
In the 1970s, Jens Juul Holst and Joel Habener began research on the GLP-1 hormone, initially in relation to duodenal ulcer disease. They were examining hormones secreted during eating, and testing them on pig pancreases, leading to the discovery of GLP-1's significant potency in 1988. Their work, which later contributed significantly to diabetes and obesity treatments, earned them and Daniel J. Drucker the 2021 Warren Alpert Foundation Prize.Research continued, and in 1993, Michael Nauck managed to infuse GLP-1 into people with type2 diabetes, stimulating insulin while inhibiting glucagon and bringing blood glucose to normal levels. However, treating diabetes with GLP-1 hormones resulted in significant side effects, leading researchers financed by Novo Nordisk to start looking to develop a suitable compound for therapeutic use. In 1998, a team of researchers at Novo Nordisk led by Lotte Bjerre Knudsen developed liraglutide, a glucagon-like peptide-1 receptor agonist that could be used to treat diabetes. This was followed by the development of semaglutide by a team of researchers at Novo Nordisk, including Jesper Lau, Thomas Kruse, and Paw Bloch.
Clinical trials and early approvals for diabetes
In June 2008, a phase II clinical trial began studying semaglutide, a once-weekly diabetes therapy as a longer-acting alternative to liraglutide. It was given the brand name Ozempic. Clinical trials started in January 2016 and ended in May 2017.The US Food and Drug Administration approved semaglutide based on evidence from seven clinical trials of 4087 participants with type2 diabetes. The trials were conducted at 536 sites in 33 countries, including Canada, Mexico, Russia, Ukraine, Turkey, India, South Africa, Japan, Hong Kong, multiple European countries, Argentina, and the United States. In two of these trials, participants were randomly assigned to receive either semaglutide or placebo injection weekly. Neither the participant nor the health care provider knew which treatment was being given until after the trials were completed. Treatment was given for 30 weeks. In the other five trials, participants were randomly assigned to receive either semaglutide or another anti-diabetic medication, and the participant and provider knew which medication was being given in four trials. Treatment was given for 30 weeks or 56 weeks. In each trial, HbA1c was measured from the start of the trial to the end of the trial and compared between the semaglutide group and the other groups.
The FDA also considered data from one separate trial of 3297 participants with type2 diabetes who were at high risk for cardiovascular events. This trial was conducted in 20 countries: multiple European countries, Russia, Turkey, Brazil, Israel, Malaysia, Mexico, Thailand, Taiwan, Canada, and the United States. The participants were randomly assigned to receive semaglutide or placebo. Neither the participant nor the health care provider knew which treatment was being given. Treatment was given for 104 weeks, and the occurrence of cardiovascular events, including heart attacks, strokes, and hospitalization due to unstable angina were recorded and compared in the two groups of participants.
Trials for obesity
In March 2021, in a phase III randomized, double-blind trial, 1,961 adults with a body mass index of 30 or greater were assigned in a 2:1 ratio to a treatment with once-weekly subcutaneous semaglutide or placebo, plus lifestyle intervention. The trials occurred at 129 sites in 16 countries in Asia, Europe, North America, and South America. The mean percentage change in body weight at week 68 was −14.9% in the semaglutide group vs −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points.A 2022 review of anti-obesity treatments found that semaglutide as well as tirzepatide were more promising than previous anti-obesity drugs, although less effective than bariatric surgery.