In 2014, liraglutide was approved as a drug for weight loss by the US Food and Drug Administration (FDA), then later by the European Medicines Agency (EMA) in 2015. It is a once-daily injected drug based on the gut hormone glucagon-like peptide-1 (GLP-1), whose biology has turned out to be a goldmine for the medical management of obesity and type 2 diabetes. Liraglutide, which was developed by Novo Nordisk, causes about 7% loss of body weight in people with obesity when paired with diet and exercise advice.

By tweaking the design of GLP-1-based drugs, Novo Nordisk discovered another drug that had a much longer half-life in the blood and a substantially larger impact on body weight: semaglutide. Semaglutide only requires one injection per week and produces average weight losses of 15-18% in people with obesity when paired with diet and exercise advice. Initially approved at lower doses for the treatment of type 2 diabetes, the FDA approved a higher dose (2.4 mg) for the treatment of obesity in June 2021. It's marketed under the brand name Wegovy in the US, and Ozempic or Rybelsus in other markets.

Given the checkered history of weight loss drugs, it's reasonable to be cautious about their safety. Semaglutide and related drugs often cause unpleasant gastrointestinal side effects like nausea, heartburn, diarrhea, constipation, fatigue, and headache, but these are typically mild and transient if the dose is started low and escalated slowly. Few people discontinue semaglutide due to side effects.

Some studies have suggested that this class of drugs may increase the risk of thyroid and pancreatic cancer in lab rodents. Yet randomized controlled trials including 64,000 people with type 2 diabetes have not observed an increased risk of cancer, overall or at any specific site in humans. These trials are limited in duration and don't yet have enough people to reliably identify modest increases in the risk of low-frequency outcomes like thyroid and pancreatic cancer. Observational monitoring data are mixed but have not provided a clear signal of increased risk.

Importantly, trials suggest that semaglutide reduces major cardiovascular events by about one quarter, similar to cholesterol-lowering statin drugs. Furthermore, across seven trials in people with type 2 diabetes, semaglutide and related drugs reduce the overall risk of dying by 12%. These findings are reassuring, but monitoring is ongoing and some concern remains.