Authorities in the US have red-flagged various diabetic drugs approved for weight loss after the Food & Drug Administration (FDA) was found to have received close on 300 reports of suicidal thoughts or behaviour from patients taking the medication.
One woman told Reuters she had felt trapped in a disturbing pattern for a year while taking Ozempic, the popular drug from Novo Nordisk, used to treat diabetes and obesity, after depression and occasional suicidal thoughts set in within days of her weekly injection.
She said she knew it was the drug as she had not previously suffered from depression.
She was one of four who told Reuters about having suicidal thoughts while taking Ozempic or Wegovy, another Novo top-seller approved for weight loss. A fifth patient said he experienced depression and suicidal thoughts after taking Mounjaro, a similar diabetes medicine from Eli Lilly, which is also used for weight loss.
All three drugs are GLP-1 receptor agonists, which slow digestion and reduce hunger.
The FDA has received 265 reports of suicidal thoughts or behaviour in patients taking these or similar medicines since 2010, Reuters found after examining the agency’s adverse-event database. Thirty-six reports describe a death by suicide or suspected suicide.
Accounts of suicidal thoughts linked to this class of drugs are drawing increasing scrutiny, including an investigation by European regulators announced in July.
The FDA said it was evaluating such reports and would decide on what action, if any, to take after a thorough review.
The Reuters review is the first exhaustive examination of FDA adverse-event reports involving incidents of suicidal thinking linked to GLP-1 drugs. The news organisation also filed public records requests for 113 more-detailed narratives for individual incidents among the 265 reports in the FDA database.
More than half of them describe suicidal thoughts appearing shortly after the person started the medicine or increased the dose.
About two fifths said symptoms ceased after they stopped taking the drug or lowered the dose.
Thirty of the 113 described patients with a history of depression, suicidal thinking or another mental health condition. Another five reports said the patient had no history of psychological issues. Most reports don’t address that medical history.
Adverse-event reports provide a warning system for the medical community but aren’t considered definitive scientific evidence.
Submitted by doctors, patients, drugmakers and others, they often lack key details and do not, on their own, establish that a drug caused the potentially dangerous health events.
In a statement, Novo said it takes “all reports about adverse events … very seriously”, and would continue to monitor clinical data and collaborate with authorities. Its own safety monitoring found no “causal association” between the drugs and thoughts of self-harm.
Eli Lilly said it was working closely with regulators on potential safety issues involving Mounjaro and would continue to review data on “suicidal ideation, thoughts of self-harm and depression”.
Dr Erick Turner, a former FDA medical officer who reviewed psychiatric drugs, said cases like these were cause for concern. Regulators should pay attention to cases where patients have no history of depression, experience suicidal thoughts suddenly after starting or increasing their dose, and then see symptoms subside after stopping, he said.
“That makes it harder to explain away the suicidality,” added Turner, a professor of psychiatry at Oregon Health & Science University. “It makes any occurrence of those safety signals more credible.”
Cause for alarm
Millions of patients are being encouraged to try drugs like Wegovy, which led to an average loss of 15% of body weight in clinical trials, making it the most effective approved weight-loss treatment to date.
Its 2021 approval kickstarted a new market for obesity drugs, estimated to reach $100bn within a decade.
Novo Nordisk says additional trials, which it plans to publish soon, show the drug can also help protect patients against heart attacks and strokes.
Trials of Mounjaro showed even more weight loss, and Eli Lilly has said it expects the FDA to approve the drug for that purpose this year.
Ozempic, Wegovy and Mounjaro have so far proved relatively safe. Their clinical trials did not show suicide risk, said the FDA. But doctors are on the lookout for previously undocumented dangers as hundreds of thousands of new patients start taking these drugs to lose weight.
Heightened suicide risks have caused regulators to issue strong warnings on obesity drugs in the past.
Wegovy’s US prescribing label, produced with FDA approval, says suicidal thoughts or attempts have been reported in clinical trials for other weight-loss medicines. It recommends that patients starting Wegovy be monitored for such behaviour and calls for those with a history of suicide attempts or active suicidal thinking to avoid the drug.
Novo’s Saxenda, a GLP-1 approved in 2014 for weight loss and included in the Reuters analysis of adverse event reports submitted to the FDA, contains an FDA warning because suicidal thoughts or behaviours were seen in some patients during clinical trials.
There’s no such language on the US label for Ozempic, which was approved for treating diabetes in 2017. Suicidal behaviour isn’t listed as a potential side effect for any GLP-1 drugs in the European Union.
Scrutiny of GLP-1 drugs intensified in July after the European Medicines Agency (EMA) announced an investigation of suicide risk from Ozempic, Wegovy, Saxenda and other GLP-1 drugs.
It later said it was analysing about 150 reports of suicidal thinking. Health agencies in the UK and Canada are also reviewing the drugs’ suicide risk. The drug manufacturers have said they are cooperating with the probes.
The European regulator expects to conclude its review in November. The agency said such reviews can result in regulators requiring a warning on the product, issuing urgent safety restrictions or asking drugmakers to conduct a more extensive safety study.
If the FDA finds that GLP-1 drugs increase suicide risk, it could also require warnings.
In the case of Wegovy, the agency could strengthen the existing warning by requiring more explicit language linking the drug to suicide risk. Its strongest action, short of banning a drug, would be to issue a so-called black-box warning, which could prompt some doctors and patients to avoid the medicine.
Novo Nordisk itself submitted 180 of the 265 reports to the FDA describing suicidal thinking or behaviours that Reuters found.
Among the 113 detailed cases, 91 were filed by Novo.
In nearly all of those, the company wrote that there weren’t enough details to determine what had happened. In three reports, the company sought to explain patients’ experiences by saying overweight people had a higher risk of depression or suicidal ideation.
Novo declined to comment further on its statements in these reports.
It’s difficult to gauge whether or how quickly such reports will spur FDA action. It took the agency 12 years after launching a safety review of the allergy-and-asthma drug Singulair before it required a black-box warning about serious neuropsychiatric side effects, including suicidal thinking, in 2020.
By then, the FDA had received more than 80 reports of people killing themselves while taking the medicine, including 31 children and teenagers.
Visions of death
GLP-1 drugs reach the brain, according to pharmacology reports Novo and Lilly submitted to the FDA. That may account for their effectiveness in influencing hunger signals, but could also increase risks of neuropsychiatric side effects.
Patients described to Reuters suicidal or panicked feelings that came on quickly after either starting the medicine or increasing the dosage.
None was aware of their experiences being reported to the FDA, underscoring how the FDA’s adverse-event database often doesn’t capture the full scope of a drug’s potential problems. Some people do not connect medical or psychological issues to their medicines.
Three of the patients described becoming scared after experiencing impulses to kill themselves by crashing their cars.
Some patients told Reuters they stuck with the therapy, despite the suicidal thoughts, because doctors assured them the drug didn’t cause them.
Others, in reports to the FDA and interviews, said they had suffered from depression in the past, but that the feelings they experienced on the GLP-1 drugs felt more intense.
One patient on Mounjaro said his dark thoughts prompted him to check himself into the psychiatric hospital where he works as a nurse. He ultimately decided to continue the medicine, however, because his blood sugar levels had improved and he had lost 30kg in five months.
He continues to feel depressed and, at times, suicidal, but says he can manage these feelings now that he is aware of the possible cause. He favours a stronger warning for consumers.
“People need to know their feelings may not be them,” he said.
See more from MedicalBrief archives:
Patients felled by weight-loss drugs’ side effects
UK reviews weight-loss drugs after 'suicidal thoughts'
European agency probes weight loss drugs’ link to suicidal thoughts
WHO warning about weight-loss drugs as obesity guidelines amended