Semaglutide is an anti-diabetic medication used for the treatment of type2 diabetes, and an anti-obesity medication used for weight management. It can be administered by subcutaneous injection or taken orally. It is sold as a generic drug by several drug companies in the Indian and Canadian markets, and worldwide by its originator, Novo, under the brand names Ozempic and Rybelsus for diabetes; under the brand name Wegovy for weight management; and under the brand names Wegovy and Kayshild for the treatment of metabolic-associated steatohepatitis (nonalcoholic steatohepatitis) and liver cirrhosis. Wegovy is also used to reduce the risk of heart attacks.
Semaglutide is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain, and acts as a GLP-1 receptor agonist. The most common side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation.
Semaglutide was approved for medical use in the United States in 2017, in Canada, the European Union and Japan in 2018, and in Australia in 2019. 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
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.
Semaglutide (as Wegovy) 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 (initial or who are overweight and have at least one weight-related comorbidity such as dysglycemia (prediabetes or type2 diabetes), 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 (aged twelve years and older) with obesity and body weight above .
Semaglutide (as Kayshild) is indicated in conjunction with diet and exercise for the treatment of adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate or advanced liver fibrosis (stage F2 or F3).
United States In the United States, 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 (as Wegovy) is indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and who are either obese or overweight; to reduce excess body weight and maintain weight reduction long term in obese individuals twelve years of age or older, or for overweight adults with at least one weight-related comorbid condition.
In August 2025, the Food and Drug Administration (FDA) expanded the indication for semaglutide (as Wegovy) to include the treatment of noncirrhotic metabolic-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults.
In October 2025, the FDA further expanded the indication for semaglutide (as Rybelsus) to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type2 diabetes who are at high risk for these events.
In December 2025, the FDA approved an oral version of semaglutide for weight management, using the same brand name (Wegovy) as the injectable version.
Contraindications Semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or in people with multiple endocrine neoplasia type2.
Adverse effects and safety profile Semaglutide can cause a variety of side effects.
Gastrointestinal dynamics The most common side effects include nausea, diarrhea, vomiting, constipation, and abdominal pain. These gastrointestinal effects are dose-dependent and mostly mild-to-moderate in severity. They are highly transient, typically peaking during the initial 8-to-12-week dose-escalation phase before waning over time. The drug delays gastric emptying, which can lead to indigestion, belching, and rarely, gastroparesis or bowel obstruction.
Gallbladder and biliary risk Semaglutide treatment is associated with an increased risk of biliary disease, specifically gallstones (cholelithiasis). While initially thought to be solely a byproduct of rapid weight loss, the exact mechanism may involve reduced gallbladder motility and changes in bile acid composition.
Pancreatic and thyroid safety Historically, GLP-1 receptor agonists have carried warnings regarding acute pancreatitis and pancreatic cancer. However, large-scale cardiovascular outcome trials for semaglutide have not found a statistically significant increase in the incidence of these conditions in humans.
The US prescription label contains a boxed warning for thyroid C-cell tumors. This warning is based on rodent studies; rodents possess a high density of GLP-1 receptors in their thyroid C-cells, which leads to hyperplasia and tumors when stimulated. In contrast, human thyroids express these receptors only marginally, making the risk of medullary thyroid carcinoma highly specific to rodents and clinically unlikely in humans. Semaglutide remains contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
Microvascular effects (retinopathy) Initial trials noted an increase in complications related to diabetic retinopathy. Subsequent analyses have clarified that this early worsening of pre-existing retinopathy is a secondary effect caused by the rapid and robust drop in blood glucose levels, rather than a direct toxic effect of semaglutide on the eyes.
Additional effects Semaglutide typically causes a benign increase in resting heart rate (around 3 beats per minute), which has not been associated with adverse cardiovascular events. In January 2026, the US Food and Drug Administration requested removal of suicidal behavior and ideation warning from glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications.
A 2024 systematic review of 6 studies found that while lean body mass was unchanged in some cases, there were instances of significant decreases in lean body mass (0–40%). However, the review concluded that in all studies the ratio of lean body mass to total body mass increased, supporting continued use of the medication.
After stopping semaglutide, individuals on average regain 67% of the weight they lost during treatment within the following year, according to a 2025 systematic review. People return to their previous weight within a year and a half on average after stopping semaglutide.
Social factors The general public's impression of semaglutide is that it is an "easy way out" to lose weight by taking a prescription instead of altering one's lifestyle. This narrative is complicated by anthropologist Sissel Due Jensen and associates' investigation of semaglutide use in three Danish general practices. According to their findings, treatment involves more than just taking medication and losing weight. Rather, in reaction to adverse effects, financial limitations, and individual circumstances, patients and clinicians constantly "tinker" with dosage, timing, and administration. Even if treatment interferes with their daily lives, patients also put considerable effort into obtaining and maintaining access to the medication.
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 (semaglutide positions 2 and 28), 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 (semaglutide position 20) 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 (albumin), which enables longer presence in the blood circulation.
Semaglutide's half-life in the blood is about seven days (165–184 hours).
Mechanism of action
Semaglutide is a glucagon-like peptide-1 receptor agonist. The drug mimicks the hormone glucagon-like peptide-1 (GLP-1), an incretin. This produces multiple effects on metabolic pathways:
Pancreatic and glycemic control Semaglutide enhances the growth and proliferation of pancreatic beta cells, which are responsible for insulin production, while mitigating oxidative stress to reduce cell death (apoptosis). It achieves glycemic control primarily through a glucose-dependent mechanism: by binding to GLP-1 receptors on beta cells, it elevates intracellular levels of cyclic AMP (cAMP) and activates protein kinase A (PKA) and related signaling pathways. This cascade alters cellular energy dynamics, ultimately triggering the influx of calcium into the cell, which prompts the exocytosis (release) of insulin-containing vesicles into the bloodstream.
Concurrently, semaglutide inhibits the release of glucagon from pancreatic alpha cell, which decreases glucose production by the liver (gluconeogenesis) and maintains blood sugar level stability, particularly preventing sharp spikes after meals. Beyond its direct action on the pancreas, semaglutide alleviates peripheral insulin resistance. It does this by upregulating phosphorylated IRS-1 and activating pathways (like AMPK/SIRT1) that promote the transport of the GLUT4 glucose transporter to cell membranes in muscle and adipose tissue, thereby increasing overall cellular glucose uptake.
Central nervous system and appetite regulation Semaglutide crosses the blood-brain barrier to interact with the arcuate nucleus of the hypothalamus, a crucial brain region for energy balance. It suppresses appetite through a dual mechanism involving hypothalamic feeding circuits. Acute administration has been shown to stimulate anorexigenic (satiety-inducing) neurons that express proopiomelanocortin (POMC) and cocaine-and amphetamine-regulated transcript (CART), while simultaneously inhibiting orexigenic (appetite-inducing) neurons that express AgRP and NPY. However, more recent evidence indicates that during chronic treatment, AgRP neurons become functionally recruited and are required for the full weight-lowering effects of GLP-1 receptor agonists in female mice, despite persistent suppression of food intake. This recruitment is associated with increased neuronal activation, synaptic remodeling, and fat utilization, suggesting that AgRP neurons contribute to the adaptive metabolic responses that sustain long-term weight loss rather than simply promoting hunger.