overweight woman talking to doctor about glp medications

In the past few years, Ozempic and Wegovy, two new weight loss medications, have been in the news quite often, both for their ability to help people manage their weight and for their association with variety of distressing side effects related to mental illness.

Recently, they’re back in the headlines for a decidedly different reason: their potential for alleviating the symptoms certain mental illnesses.

What Are These Medications?

Ozempic and Wegovy contain a substance called semaglutide, which is classified as a GLP-1 agonist. This refers to its ability to act in a manner similar to the glucagon-like peptide 1, which is a naturally occurring hormone. Among other things, GLP-1 helps regulate the levels of blood sugar in the bloodstream and control the rate at which food leaves the stomach.

Researchers developed medications in the 1970s to treat duodenal ulcer disease.

By the early 1990s, research demonstrated their effectiveness at managing the symptoms of type-2 diabetes. However, during studies requiring participants to eat a meal before an insulin level check, many participants found  they couldn’t finish their food. This led scientists to explore their usefulness as weight loss medications.

In June 2021, the U.S. Food and Drug Administration (FDA) approved Wegovy for once-a-week injections for overweight or obese adults who had at least one additional weight-related health concern.

Reports published in late 2023 and early 2024 suggested semaglutide and other GLP-1 agonists could play an important role in easing symptoms or preventing the onset of various mental illnesses.

Study: Weight Loss Medications May Help Mental Illness

In a study published in February 2024 on the mental health benefits of GLP-1 drugs, two research teams worked separately and simultaneously to assess the mental health benefits of five GLP-1 agonist medications:

  • Dulaglutide (Trulicity)
  • Exenatide (Byetta, Bydureon)
  • Liraglutide (Victoza)
  • Semaglutide (Ozempic, Wegovy)
  • Tirzepatide (Mounjaro)

The researchers analyzed data from about three million patients with diabetes and about one million non-diabetic patients who took at least one of these medications. The research team compared to information from a control group of patients who had not taken any of the medications.

Both research teams reached similar conclusions about the impact of GLP-1 agonists on anxiety and depression. Highlights of their findings include:

  • For participants with diabetes, anxiety rates were 60% lower among those who took tirzepatide than among those who didn’t.
  • In the diabetes group, patients who took tirzepatide were 65% less likely to receive a diagnosis for a depressive disorder than were patients who didn’t.
  • Participants with diabetes who took semaglutide were 44% less likely to receive a diagnosis for with and 45% less likely to report depression, compared to patients with diabetes who didn’t take semaglutide.
  • Non-diabetic patients who took semaglutide reported rates of depression 37% lower than non-diabetic patients who didn’t take semaglutide.
  • Semaglutide use correlated with a 31% reduction in anxiety diagnoses among the non-diabetic patients.
  • Liraglutide use correlated with a 13% reduction in anxiety among diabetic patients, but showed no significant effect on anxiety among non-diabetic patients.
  • Liraglutide had no impact on rates of depression diagnoses in either group.

In an article in Medical News Today, Dr. Kathryn Basford noted the importance of these findings:

“The results suggest a potentially new therapeutic benefit of GLP-1 medications beyond their established use for glucose control and weight management.”

Reports Warn of Negative Effects

Unfortunately, the news about weight loss medications and mental illness isn’t all positive.

In October 2023, Reuters published an investigation into reports of increased suicidal ideation among people taking Ozempic and similar drugs.

The article included the following details.

Reuters Report: Questions about Semaglutides

  • Between 2010-2023, the FDA received 265 reports of patients who experienced suicidal thoughts or behaviors while taking a GLP-1 medication. These reports included 36 deaths by suicide or suspected suicide.
  • More than 50% of the reports involved patients who first had suicidal thoughts after taking the medication, and 40% included patients who said the thoughts subsided after they ended or significantly reduced their use.
  • In July 2023, after receiving 150 reports of suicidal ideation among patients taking semaglutides, the European Medicines Agency (EMA) opened an investigation into the suicide risk these medications present.

In January 2024, the National Institutes of Health (NIH) released the results of a study that contradicted the concerns raised in the Reuters article.

The NIH study, conducted by a team under the direction of Dr. Rong Xu of Case Western Reserve University and Dr. Nora Volkow, Director of the National Institute on Drug Abuse (NIDA), included a review of electronic health record data from 1.75 million patients who reported overweight, obesity, or type-2 diabetes.

The research team reported the following:

  • Among patients who took semaglutide for weight loss, 0.11% reported suicidal thoughts within the first six months.
  • Among patients who took a non-GLP-1 medication for weight loss, 0.43% reported suicidal thoughts within six months, a rate four times higher than the semaglutide group.

When researchers focused on the patients who reported suicidal thoughts before receiving weight loss medication, they found:

  • 6.5% had suicidal thoughts after taking semaglutide.
  • 14.1% of patients taking non-GLP-1 drug said they had suicidal thoughts after initiating the medication, twice the rate in the semaglutide group.

Data from type-2 diabetes patients followed a similar pattern, with lower rates of suicidal ideation among those taking semaglutide.

Dr. Volkow characterizes these findings as follows:

“Our study suggests semaglutide can be safe for those with mental health conditions. As researchers are also investigating semaglutide as a treatment for substance use disorders – which often co-occur with other mental health disorders – it is vital to ensure the medication is safe and does not place vulnerable groups at even greater risk of harmful health impacts.”

How Will This Affect Treatment?

Currently, neither Ozempic, Wegovy, nor any of the other GLP-1 medications discussed above are FDA-approved to treat anxiety, depression, or other mental health disorders.

However, reports indicate medical professionals prescribe these weight loss medications on an off-label basis for people with certain types of mental illness. If research indicates a medication may help, and both patient and provider discuss and understand the potential risks and benefits of the medication, off-label use by qualified healthcare providers is legal in the U.S.

Additional research is required to determine both the benefits and potential risks of prescribing semaglutide or other GLP-1 drugs to treat mental illnesses.

In the interim, patients who take these medications for any purpose – including for type-2 diabetes, weight control problems, or mental health concerns – should speak with their doctor immediately if they experience any negative physical or psychological side effects.