When Wegovy (generic name semaglutide), the obesity drug from Denmark's Novo Nordisk, is administered at three times the standard dose, 7 out of 10 people experience side effects. Not only the previously known gastrointestinal issues but also sensory abnormalities appeared. Experts warned that increasing the dose of obesity drugs to boost weight-loss effects can lead to serious side effects.
A research team led by Sean Wharton, a professor at the University of Toronto in Canada, and Maria Kabisch, a researcher at Novo Nordisk, said in The Lancet Diabetes and Endocrinology on 14th (local time) that "when 7.2 mg of semaglutide was administered weekly, 71% experienced side effects."
Wegovy is a glucagon-like peptide (GLP)-1 class obesity drug. GLP-1 is a hormone secreted by the small intestine after meals that promotes the secretion of insulin, which lowers blood sugar, in the pancreas and suppresses glucagon, which raises blood sugar. Drugs that mimic this were originally developed as diabetes treatments to lower blood sugar, and later evolved into obesity treatments once their weight-loss effects were confirmed. Semaglutide, which mimics GLP-1, reduces appetite in the brain and slows the rate at which food leaves the stomach, increasing satiety.
The researchers administered Wegovy to about 1,400 adults in 11 countries, including the United States, Canada, Germany, and Norway. The clinical trial participants had an average age of 47 and an average body weight of 113 kg. Participants were randomly assigned to receive weekly injections of Wegovy at 7.2 mg or 2.4 mg, or a placebo (dummy drug).
Wegovy dosing comes in five options: 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg. In this clinical trial, participants started at 0.25 mg and increased to 2.4 mg by week 16. From week 20, some increased the dose to 7.2 mg for 52 weeks. The rest either continued at 2.4 mg or received a dummy drug.
The researchers examined weight loss and side effects when administering the standard dose (2.4 mg) and a high dose (7.2 mg), which is three times that amount. Analysis showed that those who received the standard 2.4 mg weekly lost an average of 16% of their body weight. Those who received the high 7.2 mg dose lost 19%.
Weight loss came with side effects. Among those who received the standard 2.4 mg dose, 61% experienced nausea, vomiting, or diarrhea. Among those who received the high 7.2 mg dose, 71% experienced side effects.
In particular, among those who received the high dose, 23% experienced sensory abnormalities. They felt skin pain, discomfort, and a burning sensation. Among those who received the standard dose, 6% did, and among those who received the dummy drug, only one person experienced such sensory abnormalities. The researchers noted, "In the 7.2 mg group, four people discontinued treatment due to sensory abnormalities," adding, "In the 2.4 mg group and the dummy drug group, zero people discontinued treatment."
References
The Lancet Diabetes and Endocrinology (2025), DOI: https://doi.org/10.1016/S2213-8587(25)00226-8