EMA probes suicide risk with Novo Nordisk obesity drugs

The European Medicines Agency (EMA) has started a review of two Novo Nordisk drugs used to treat obesity and those overweight, following reports of suicidal thoughts or self-injury in a small number of patients taking them.

The investigation by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is initially focusing on two of the Danish drugmaker’s GLP-1 agonists – semaglutide and liraglutide – but in time could be extended to include other drugs in the class, according to the EU regulator.

It has been prompted by a report from the Icelandic Medicines Agency that said it had identified three cases of suicidal thinking or self-harm among patients taking Ozempic – a formulation of semaglutide approved to treat diabetes – or liraglutide-based weight-loss therapy Saxenda.

Semaglutide is also used in oral diabetes therapy Rybelsus and once-weekly weight-loss injectable Wegovy, while liraglutide is the active ingredient in diabetes medicines Victoza and Xultophy. According to the EMA, there has been one case each of suicidal thoughts with Ozempic and Saxenda, and one further case of self-injury in a Saxenda user.

Suicidal behaviour isn’t listed as a possible side effect on EU documentation for either of the two drugs, but in the US the situation is a little different.

Suicidal thinking and self-harm aren’t currently listed on the FDA-approved prescribing information for Ozempic or as possible adverse reactions. However, for Saxenda, as well as Wegovy, entries in the warnings and precautions section mention “suicidal behaviour and ideation”, with a recommendation to monitor patients for “depression or suicidal thoughts”.

According to the FDA, that is a standard requirement for any drug used to achieve weight loss that works on the central nervous system.

That stems in part from experience with an earlier weight-loss drug from Sanofi called Acomplia/Zimulti (rimonabant), which was approved in Europe in 2006, but withdrawn from sale two years later after the EMA concluded it was associated with a risk of serious psychiatric problems, including suicide. It was never approved by the FDA.

Novo Nordisk, meanwhile, says its own safety monitoring has not identified any “causal association” with the side effects, pointing out that GLP-1 agonists “have been used to treat type 2 diabetes for more than 15 years and for treatment of obesity for eight years.”

It added that it is continuously monitoring patients in trials, as well as those taking its drugs in real-world settings, and working with regulators to ensure patient safety, and “remains confident in the benefit/risk profile of the products.”

If the PRAC does widen its investigation to include other drugs acting on GLP-1, it could extend to other products, including Eli Lilly’s Trulicity (dulaglutide) for diabetes and dual GIP/GLP-1 agonist Mounjaro (tirzepatide), which is approved for diabetes and in late-stage development for obesity.