In light of suicidal ideation risk, can we make a 'better' Ozempic?
Key Takeaways
Ozempic (semaglutide) has gained attention for its weight loss effects—but also for negative side effects, such as gastrointestinal issues and mental health concerns.
A recent study in JAMA detected a signal of suicidal ideation with semaglutide, prompting calls for urgent clarification and triggering reviews by regulatory agencies like the FDA and the European Medicines Agency.
Research is ongoing to develop GLP-1 receptor agonists (a new and improved Ozempic, if you will) that could promote weight loss without inducing nausea, while the association between semaglutide and suicidal ideation requires further investigation to establish causality.
Semaglutide, a GLP-1 receptor agonist, is approved by the FDA under three separate brand names—Ozempic, Rybelsus, and Wegovy—each with its own approved indications for use.
Ozempic in particular has captured news headlines for a number of reasons over the past year, not only due to its skyrocketing popularity as a weight loss drug, but also because of its potential side effects.
While the drug has many benefits, these side effects can be severe—and new research shows promising potential for the development of a GLP-1 formulation that maximizes the therapeutic advantages while minimizing adverse effects.
Side effects impact quality of life
Ozempic is known to cause nausea and vomiting along with the feelings of early satiety and gastric fullness, induced as part of its weight-loss mechanism of action.
However, more recently, mental health side effects have become a topic of concern when assessing Ozempic’s safety profile. These include social-media reports of mood deterioration, increased anxiety and/or insomnia, and even suicidal ideation.[]
Related: 'Ozempic personality' and the psychological toll of GLP-1s
In a 2024 study published in JAMA, investigators reported their results of a disproportionality analysis conducted through case-control design, based on the database of suspected adverse drug reactions from the WHO.[] In this analysis, they found a “disproportionality signal of suicidal ideation with semaglutide, which remained significant when comparing semaglutide with dapagliflozin and metformin and in the subgroup of patients with coreported use of antidepressants and benzodiazepines.”
Due to these results, the study authors concluded this finding “warrants urgent clarification.”[]
Nausea study paves the way
In animal-based studies (with ethical repercussions[]), a research team at the Monell Chemical Senses Center in Philadelphia identified a group of neurons in the brains of live mice that manage food consumption without inducing nausea.[]
As the study authors described their findings, “We investigated the brain circuits that link satiety to aversion, and unexpectedly discovered that the neural circuits mediating these effects are functionally separable.”
The investigators believe these findings hold promise for further development of GLP-1s’ action on neurons “that could be selectively targeted to promote weight loss while avoiding the adverse side effects that limit treatment adherence.”[]
Addressing suicidal ideation risk
The recent findings of increased suicidal ideation associated with Ozempic use have raised alarms globally, and Novo Nordisk’s GLP-1 drugs are under review by the European Medicines Agency (EMA) due to these and similar reports.[] The EMA review, for instance, was initially triggered by the Icelandic Medicines Agency, secondary to reports of suicidal ideation and even self-injury in patients taking liraglutide or semaglutide.
The JAMA study, it should be noted, did not detect a signal of suicidal ideation with liraglutide; this was only found to be the case with semaglutide; importantly, the analysis also included patients who were potentially using GLP-1s off-label.
Experts caution that association is not causality, and that further investigation is needed. It does appear that such investigation will be ongoing; in the United States, 201 reports of suicidal ideation have been received so far by the FDA from users of semaglutide or Eli Lilly’s tirzepatide, and these reports have resulted in an FDA probe.[]
What this means for you
Findings of a new study into semaglutide-associated suicidal ideation underscore the importance of careful patient monitoring when prescribing Ozempic or other semaglutide medications. Among other research, it’s also prompted a more concerted focus into developing a GLP-1 that can deliver the benefits with less severe side effects. It's crucial to stay informed about ongoing investigations and regulatory updates regarding these medications, and consider implementing additional mental health screening or follow-up for patients using semaglutide, particularly those with a history of depression or other mental health conditions.