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Prediction market on metaculus. GLP-1 receptor agonistsl originally approved for type 2 diabetes starting with exenatide (Byetta) in 2005, have expanded into one of the largest drug classes in modern pharmaceutical history, driven primarily by their weight-loss efficacy. Semaglutide, tirzepatide, and liraglutide are now FDA-approved for obesity as well as diabetes, and Wegovy has additionally been approved for cardiovascular risk reduction following the SELECT trial, which showed a 20% reduction in major adverse cardiovascular events. Usage has scaled from a few million U.S. patients in 2023 to an estimated 10 million in 2025, with analyst projections around 25 million by 2030. As of mid-2026, several safety signals for GLP-1s remain under active investigation: * A thyroid C-cell tumor warning remains on the label as a class-wide boxed warning, though the underlying mechanism has been demonstrated in rodents but not confirmed in primates, and its relevance to human risk remains uncertain after roughly two decades of clinical use for the earliest drugs in the class. [nih](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11050669/) * A NAION (vision loss) signal for semaglutide has prompted an EU label update, though FDA action on this specific signal is still evolving. * A network meta-analysis of 68 randomized controlled trials covering over 207,000 participants found a dose-dependent association between high-dose injectable semaglutide and colorectal tumor incidence, which the authors describe as a signal requiring further validation rather than a confirmed causal risk.  * Rare but severe gastrointestinal motility events, gastroparesis, ileus, bowel obstruction, continue to generate case reports and are the subject of ongoing litigation: as of an April 2026 JPML report, a consolidated multidistrict litigation over gastrointestinal injuries had 3,546 pending actions in the Eastern District of Pennsylvania, still in early discovery. [The RX Index](https://therxindex.com/guides/glp-1-long-term-side-effects/) * A large real-world cohort study found an elevated risk of vestibular disorders in both semaglutide and tirzepatide users compared to controls, with hazard ratios in the range of 4–5x by three years of follow-up, though absolute incidence remains low (under 0.5%). * [https://www.forbes.com/health/weight-loss/glp-1-statistics/](https://www.forbes.com/health/weight-loss/glp-1-statistics/)  * [https://www.jpmorgan.com/insights/global-research/current-events/obesity-drugs](https://www.jpmorgan.com/insights/global-research/current-events/obesity-drugs)  * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11050669/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11050669/)  * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825905/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825905/)  * [https://therxindex.com/guides/glp-1-long-term-side-effects/](https://therxindex.com/guides/glp-1-long-term-side-effects/)  * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109458/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109458/)  * [https://www.healthline.com/health-news/compounded-weight-loss-drug-ban-ozempic-zepbound](https://www.healthline.com/health-news/compounded-weight-loss-drug-ban-ozempic-zepbound)  * [https://www.pharmacytimes.com/view/fda-moves-to-restrict-mass-marketed-compounded-glp-1-products](https://www.pharmacytimes.com/view/fda-moves-to-restrict-mass-marketed-compounded-glp-1-products) 
Resolves: 12/31/2034.