EMA Investigates Possible Suicide Risk of Some Diabetes and Weight-Loss Drugs

The European Medicines Agency (EMA) is investigating Novo Nordisk’s diabetes drug Ozempic and weight-loss treatment Saxenda after Iceland’s health regulator flagged three cases of patients thinking about suicide or self-harm.

The review is expected to be concluded in November 2023

An EMA safety committee is looking into adverse events raised by the Icelandic Medicines Agency, including two cases of suicidal thoughts in those who used Ozempic, which contains the active ingredient semaglutide, and Saxenda, the regulator said.

EMA’s safety committee, the PRAC, is reviewing data on the risk of suicidal thoughts and thoughts of self-harm with medicines known as GLP-1 receptor agonists,1 including Ozempic (semaglutide), Saxenda (liraglutide) and Wegovy (semaglutide). These medicines are used for weight loss and for treating type 2 diabetes.

The review was triggered by the Icelandic medicines agency following reports of suicidal thoughts and self-injury in people using liraglutide and semaglutide medicines. So far authorities have retrieved and are analysing about 150 reports of possible cases of self-injury and suicidal thoughts.

Liraglutide and semaglutide medicines are widely used, with an exposure of over 20 million patient- years to date. It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors.

The review is being carried out in the context of a signal procedure. A signal is information on a new adverse event that is potentially caused by a medicine or a new aspect of a known adverse event that warrants further investigation. The presence of a signal does not necessarily mean that a medicine caused the adverse event in question.

The review of Ozempic, Saxenda and Wegovy started on 3 July 2023 and has now been extended to include other GLP-1 receptor agonists. This review is expected to be concluded in November 2023.

Novo Nordisk said patient safety was top priority

Saxenda and Wegovy are authorized for weight management, together with diet and physical activity in people who are obese or overweight in the presence of at least one weight-related health problem. Ozempic is authorized for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise but has been used off-label for weight loss. Suicidal behaviour is not currently listed as a side effect in the EU product information for any GLP-1 receptor agonists.

According to Reuters, another patient on Saxenda, Novo’s earlier and less effective weight-loss drug that contains the active ingredient liraglutide, reported thoughts of self-injury.

Novo Nordisk is known for its efforts to find ways to improve diabetes treatments. Back in 2019, Novo Nordisk announced U.S. Food and Drug Administration (FDA) approval for Rybelsus® (semaglutide) tablets 7 mg or 14 mg for adults with type 2 diabetes. In June, the company acquired BIOCORP is a French company specialized in the design, development and manufacturing of delivery systems and innovative medical devices, including Mallya, a Bluetooth enabled smart add-on device for pen injectors. 

Novo Nordisk said patient safety was top priority and it treated all reports about adverse events very seriously. Its own safety monitoring so far found no “causal association” between the self-harming thoughts and the drugs, it said in a statement.

The EMA’s investigation centers on medicines that contain either semaglutide or liraglutide. Novo’s obesity treatment Wegovy, for which demand has surged in the United States, contains semaglutide.

The review was announced weeks after the regulator raised a thyroid cancer safety signal, a means to monitor potentially adverse effects, on several of Novo’s products containing semaglutide.

Suicidal thoughts are not listed as a side effect in the EU product information for either drug, but In the United States, it is recommended that patients taking Wegovy be monitored for suicidal thoughts or behaviour.

60 reports of suicidal ideation since 2018 from patients on semaglutide, FDA says

According to the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard, there have been at least 60 reports of suicidal ideation since 2018 from patients on semaglutide or their health care providers.

FAERS has received at least 70 such reports since 2010 from users of liraglutide or their health care providers.

Information in these reports has not been verified and the existence of a report is not proof of causation, according to the FDA, but they monitor the safety of drugs throughout their life cycle. Wegovy’s trials did not suggest increased risk of suicidal behavior, but the drug’s label contains a warning for suicidal behavior and ideation because of risks associated with other weight management drugs, the regulator said.

Only three cases have been flagged by Iceland’s regulator, but the issue of suicidal thoughts linked to weight-loss drugs is sensitive and there is a history of previous such issues in other attempts by the drug industry to develop lucrative weight-loss drugs. Also, considering how small Iceland’s population is, even a few cases are cause for concern. 

Other concerns include the withdrawal of Sanofi’s Acomplia, which never won U.S. approval, in 208, after being linked to suicidal thoughts. Acomplia was designed to modify parts of the nervous system that regulate appetite. New weight-loss drugs such as Wegovy regulate appetite by mimicking a gut hormone, and not directly interfering with brain chemistry. 

Another concerns is that, in clinical trials for Ozempic and Saxenda, Novo excluded people with a history of psychiatric disorders or recent suicidal behavior.

Diet pills Contrave by Orexigen Therapeutics and Qsymia by Vivus Inc, approved in the U.S. in 2014 and 2012, respectively, carry warnings on their labels about increased risk of suicidal thoughts.

The EMA said July 10th it would consider whether the review should be extended to other medicines of the same class, known as GLP-1 receptor agonists. The EMA’s ongoing thyroid cancer investigation includes all GLP-1s.

Other drugs in the class include Eli Lilly and Co’s Mounjaro, AstraZeneca’s Bydureon and Sanofi’s Lyxumia.