What are the main long-term risks of Wegovy beyond 2 years?

The short version: beyond two years, the evidence on Wegovy's risks is almost entirely absent, and what little exists points to gallbladder disease and a theoretical thyroid cancer signal that was never adequately studied.

The longest trial in the evidence that tracks Wegovy's specific 2.4 mg dose is the STEP 5 trial, which ran for 104 weeks (just under two years) [3]. That is the outer edge of the data. Beyond that point, there are no published randomized controlled trials following people on the drug. The SELECT trial followed 17,604 patients for a mean of about 40 months, but those patients had established cardiovascular disease and were not representative of the general obesity population [4]. The SELECT trial also reported no new harms beyond what was already known, but "no new harms" in a trial that compared the drug to placebo, not to no treatment, is a weak statement [4].

The one risk that does show up in the longer-term data is gallbladder disease. The systematic review covering over 400,000 patients found gallbladder events in about 1.8% of users [4]. That is consistent with what GLP-1 drugs do: they slow stomach emptying and alter bile composition, which can cause gallstones. The meta-analysis on ursodeoxycholic acid for preventing gallstones during weight loss showed that rapid weight loss itself is a risk factor, and the drug amplifies it [5]. For a person on Wegovy for years, the risk of needing gallbladder surgery is real and not trivial.

The thyroid cancer question remains unresolved. The FDA boxed warning about C-cell tumors comes from animal studies, not human trials. The 2025 case report of rapid papillary thyroid cancer progression in five weeks is a single case, not a population signal [2]. But the manufacturer-funded trials were not powered to detect rare cancers, and no long-term registry exists to track this. The evidence simply does not answer whether five or ten years of GLP-1 receptor stimulation increases thyroid cancer risk in humans.

What the evidence also does not answer: what happens to the person who stays on Wegovy for five or ten years. The longest trial is two years [3]. The weight returns when you stop [1]. The drug alters gut motility, nutrient absorption, and pancreatic enzyme release for as long as you take it. No study has followed people long enough to see whether chronic GLP-1 receptor agonism causes pancreatitis, pancreatic cancer, or nutritional deficiencies. The manufacturer has no incentive to run that study, and the regulator did not require it.

My call: the evidence beyond two years is too thin to call Wegovy safe for chronic use, and the gallbladder risk is the one concrete harm the data does show. Confidence: low, because the question itself has not been studied.