Wegovy

The short version: Wegovy produces real weight loss on the scale, but the evidence on long-term safety and what happens after you stop is thin, and the mechanism raises questions the trials were not designed to answer.

Wegovy (semaglutide 2.4 mg weekly) is a GLP-1 receptor agonist. It works by slowing stomach emptying and signaling the brain that you are full. The STEP trials, funded by the manufacturer Novo Nordisk, show that people with obesity lose about 15% of their body weight over 68 weeks compared to about 2.5% on placebo [1, 2]. In the STEP 5 trial, that held at 15.2% versus 2.6% over two years [4]. Those are real numbers on the scale. But weight loss is a surrogate endpoint. The trials did not measure whether Wegovy reduces all-cause mortality or heart attacks in people without diabetes. The cardiovascular benefit was shown for the lower 1.8 mg dose in diabetics (the LEADER trial), not for the 2.4 mg weight-loss dose in non-diabetics [10]. That gap matters.

The safety picture is where the evidence gets thin. Gastrointestinal side effects are common: nausea in about 38% of Western patients, vomiting in 15%, and constipation in 16% [5]. A 2025 case report documented rapid progression of papillary thyroid cancer within five weeks of starting semaglutide [3]. GLP-1 receptors are expressed on thyroid cells, and animal studies have shown C-cell tumors. The FDA boxed warning about thyroid C-cell tumors exists for a reason. A single case proves nothing, but it is a signal the manufacturer-funded trials were not powered to detect. The systematic review covering over 400,000 patients found gallbladder events in about 1.8% and vision-threatening retinopathy progression in 3% of Western patients [5]. These are not rare events.

The most important finding for the person considering this drug: when you stop, the weight comes back. In the STEP 1 extension, participants regained 11.6% of their lost weight after withdrawal [1]. That is not a failure of the drug. It is a feature of a drug that suppresses appetite while you take it and stops suppressing appetite when you do not. The question nobody has answered is what happens to the person who stays on it for ten years. The longest trial in the evidence is two years [4]. There is no long-term safety data for chronic use in non-diabetics. The manufacturer has no incentive to run that study, and the regulator did not require it.

My call: Wegovy produces meaningful short-term weight loss, but the evidence does not establish long-term safety, the weight returns when you stop, and the thyroid cancer signal deserves more investigation than it has received. Confidence: moderate for short-term efficacy, low for long-term safety.