Semaglutide

In the European Union, semaglutide is indicated for the treatment of adults with insufficiently controlled type 2 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 BMI ≥ 30 kg/m) or who are overweight (initial BMI ≥ 27 kg/m) and have at least one weight-related comorbidity such as dysglycemia (prediabetes or type 2 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 60 kg (130 lb).

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).

In the United States, semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and to reduce the risk of major adverse cardiovascular events in adults with type 2 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 …

Semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or in people with multiple endocrine neoplasia type 2.

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.

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.

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.

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.

Semaglutide typically causes a benign increase in resting heart rate (around 3 beats per minute), which has not been associated with adverse cardiovascular events. …

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.

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).