Nearly three months into taking Ozempic for diabetes, Jenny Kent had already lost 12 pounds, and her blood sugar numbers were looking better than they had in a while.

Ozempic, the injectable drug approved for Type 2 diabetes, has taken the world by storm.

Despite not being approved by the Food and Drug Administration for weight loss, Ozempic has prompted people on TikTok and Instagram to speculate about which stars have used it to shed pounds seemingly overnight.

The drug has become so popular that it's been in short supply for much of the past year.

But for Kent something else changed after she started taking Ozempic.

"I was just constantly in a state of being overwhelmed," says Kent. "So my response to that was just I was just crying all the time. Sobbing, crying ... I still didn't put it together, so I kept ... taking my injections."

She's one of many people taking Ozempic and related drugs who describe mental health problems. But that side effect isn't mentioned in Ozempic's instructions for use, or drug label. Are the problems a coincidence or related to the drug?

European regulators investigate mental health reports

In July, the European Medicines Agency said that it was looking into the risk of thoughts of self-harm and suicidal thoughts with the use of Ozempic and similar drugs. As of July 11, the regulator, Europe's FDA, was evaluating more than 150 reports.

The FDA hasn't taken that step. For now, the agency is monitoring the situation. "We continue to conclude that the benefits of these medications outweigh their risks when they are used according to the FDA approved labeling," spokesperson Chanapa Tantibanchachai said in an email to NPR. She noted that weight-loss drug Wegovy, which contains the same active ingredient as Ozempic, semaglutide, includes a warning about suicidal thoughts on its label.

NPR analyzed the FDA's adverse event reporting system, or FAERS, and learned that the agency has received 489 reports of patients experiencing anxiety, depression or suicidal thoughts while taking semaglutide drugs, including Ozempic, Wegovy and Rybelsus.

In 96 of those reports, the patient had suicidal thoughts. Five of them died. It isn't known if Ozempic and the other drugs caused the mental health problems. The FDA database can flag questions but isn't designed to answer them.

"It's a passive surveillance system where people like you and me – patients, caregivers, medical providers – can report a safety event if they feel that that patient has suffered an adverse outcome from a drug that they had been on," says Rishi Desai, an assistant professor at Harvard Medical School who studies drug side effects.

The FDA database is voluntary, unverified by the agency and may have duplicates. As a result, it has no denominator or comparison group to tease out whether adverse events – like suicidal thoughts – are the result of a drug or something else.

"It could also be the case that the underlying indication, for example, which is obesity, is also known to have a higher risk for mental health issues," he says. "So we need to carefully account for that. And this database is actually not able to do that."

Despite its weaknesses, the FAERS database is still a critical tool for the FDA, says the agency's Tantibanchachai. FDA uses what it finds in FAERS to do more research and, in some cases, make changes to the instructions for doctors and patients.

"FAERS data are particularly useful for identifying new (i.e., unexpected or unlabeled), rare, serious adverse events that are temporally associated with a product for which the background rate of events is low," she wrote in an email to NPR.

She explained that these kinds of incidents often don't happen during the drug's clinical trials because those studies include relatively small numbers of patients who are taking the drug for a limited time. Once a drug is on the market, millions of patients might take it for years.

Previous clinical studies offer few answers

There's another limitation to the preapproval studies: Who gets to be part of them. Dr. Amy Rothberg, an endocrinologist at the University of Michigan, says patients recruited for the Ozempic clinical trials were screened for depression, anxiety and suicidal thoughts. They would have been excluded from participating.

"You know, that's not necessarily what goes on in clinical practice," she says. "And so there are going to be people who have major depressive disorder, who may be getting treatment, but may have an enhanced susceptibility to having worsening anxiety or depression on these drugs that we just did not account for."

After, reviewing the FAERS reports NPR found, Rothberg said almost every patient listed had an underlying major health condition that, based on the database alone, would make it hard to determine whether the drug caused the suicidal thoughts.

Even though the link between these drugs and mental health concerns isn't definitive, it's important that patients talk with doctors if they experience something unusual, says Dr. Jonathan Alpert, who chairs the Department of Psychiatry and Behavioral Sciences at Montefiore Medical Center and Albert Einstein College of Medicine.

"I always think it makes sense to take side effects like that seriously, particularly in drugs that are relatively new and that we're still learning about," he says.

Novo Nordisk spokesperson Allison Scheider says the company takes all reports about new side effects "very seriously," but added that this class of drugs has been used for more than 15 years.

"Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals," she says. "Novo Nordisk remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety."

What happened to Jenny Kent?

After a month and a half of taking Ozempic, Jenny Kent said her mental health troubles had started to affect her whole life. At work, she'd find herself reacting to run-of-the-mill requests as if she was being unjustly fired. She began withdrawing from her friends and hiding her feelings from her family.

"I was starting to feel like I was just this negative burden for everybody," she says.

Then she got a text from her younger sister, Jackie, after a belated Father's Day gathering in July: "Are you OK?"

At first, Jenny said she was fine. But after some prodding, she caved.

"I started talking to her about it, and she is the one who said, 'The only thing that's changed for you is Ozempic.' " Jenny recalls. "She's like, 'Are you sure it's not that?' And I said, 'There's no way it could be that.' "

They went back and forth like that for a while, with Jackie pressing Jenny to consider stopping Ozempic and Jenny resisting, because in all other respects the drug was working for her.

Once Jenny and Jackie started looking for information online about Ozempic and mental health, they learned about the investigation by European regulators. They also found other U.S. patients who shared experiences like Jenny's on social media.

Jenny went back to her doctor, and they decided she should stop taking Ozempic. It has only been a few months, but she says her mental health is improving bit by bit.

She says she can't be sure if stopping Ozempic is the reason, but she feels better.

"I'm kind of checking in with myself a lot," she says. "I am still pretty quick to become very irritated. Like little things will just kind of trigger me in a way that they wouldn't before. So that is still happening. I'm not crying every day."

Jackie told NPR the difference in her sister after she stopped taking Ozempic was "night and day."

"She's laughing," Jackie says. "I realized I hadn't heard her genuinely laugh in a while."

If you or someone you know may be considering suicide or is in crisis, call or text 9 8 8 to reach the Suicide & Crisis Lifeline.