UK side-effect reports list 98 fatal outcomes for tirzepatide and 37 for semaglutide

The UK's Yellow Card side-effect reporting scheme has logged about 150,000 reports of adverse reactions and serious side effects from GLP-1 medications, and more than 150 of those reports involved a fatal outcome, according to figures from the Medicines and Healthcare products Regulatory Agency (MHRA) ^[1].

Tirzepatide, sold as Mounjaro, accounted for the largest share. The MHRA data show 100,810 reports of adverse reactions for tirzepatide, 10,434 of them classified as serious, and 98 reports with a fatal outcome ^[1]. Semaglutide, sold as Wegovy, had 44,073 reports of adverse reactions, 4,892 serious reports and 37 reports with a fatal outcome ^[1]. Liraglutide, sold as Saxenda, had 3,021 reports of adverse reactions, 734 serious reports and 18 fatal outcomes in the MHRA table ^[1]. Published accounts of the same figures differ on that last point: the text accompanying the data says liraglutide had 37 fatal outcomes, while the table lists 18 ^[1].

The scheme also breaks out the types of reactions reported. For semaglutide, 28,884 reports described gastrointestinal reactions and more than 5,000 described nervous system disorders ^[1]. For tirzepatide, 65,024 reports described gastrointestinal reactions, 13,964 described nervous system disorders and more than 2,000 described psychiatric disorders ^[1]. For liraglutide, 1,461 reports described gastrointestinal reactions ^[1]. Weight-loss drugs have also been linked in reports to heart and vascular disorders, eye conditions and more serious gastrointestinal problems that had fatal outcomes ^[1].

The MHRA says the counts cannot be read as proof that the drugs caused the problems. Fatal outcomes, it said, "are not necessarily caused by the medication and could be caused by another issue, such as an undiagnosed illness or condition or using unregulated treatments" ^[1]. Reports can be filed by patients, relatives or doctors, and more than one report can be filed per patient, so the figures are not counts of individual people ^[1]. The agency also said millions of GLP-1 prescriptions are issued in the UK and that these reports make up a small fraction of them, and that the number of reports for a drug can be influenced by wider use and greater awareness of possible side effects ^[1]. The MHRA said: "On the basis of the current evidence, the benefits of GLP-1 receptor agonists outweigh the potential risks when used in line with their authorised uses" ^[1].

Manufacturers also responded to the figures. Novo Nordisk, which makes semaglutide products including Wegovy, said medicines used for chronic conditions can have side effects that vary from person to person, and that they should be prescribed and used under the supervision of a healthcare professional, who can weigh benefits and risks for each patient ^[1]. Eli Lilly, which makes Mounjaro, said it monitors, evaluates and reports safety information for its medicines, and that patients taking tirzepatide, "like with any other prescription medicine, may experience adverse events" ^[1].

Why it matters for patients

The figures come from the UK, and they count reports rather than measure risk. The data do not show how many people took each drug, so they cannot be used to compare the safety of tirzepatide, semaglutide and liraglutide against one another ^[1]. The MHRA's own caution points the same way: report volumes are shaped by how widely a drug is used and how much attention it receives ^[1]. Whether US reporting data show a similar pattern has not been reported.

The reactions reported for these drugs include common digestive issues such as nausea, vomiting, diarrhea, constipation and acid reflux, as well as less common heart, nervous system, eye and gastrointestinal problems ^[1]. The MHRA says it keeps the safety of GLP-1 medicines under continual review and that any update would be communicated promptly to patients and healthcare professionals ^[1].

What happens next

The MHRA has not announced a date for any change to its safety advice, and no new restriction on GLP-1 prescribing was disclosed alongside the figures ^[1]. The agency said any potential update on the safety of these medicines would be communicated promptly and that appropriate steps would be taken to address any identified risk ^[1].