Emerging evidence suggests GLP-1 diabetes and obesity drugs may benefit the mind as well as the body.
While the study doesn’t prove that GLP-1s were directly responsible for these improvements, experts say the findings are encouraging and match what they often see among their patients
GLP-1s Linked to Improvements in Depression, Anxiety, and Suicidal Behavior
The study followed nearly 100,000 Swedish adults with type 2 diabetes and depression, anxiety, or both. About one-fifth of them were taking one of the following GLP-1 drugs: semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), exenatide (Byetta, Bydureon), or dulaglutide (Trulicity).
To examine the mental health effects of GLP-1s, researchers looked at outcomes during periods when participants were taking the medications and periods when they weren’t. Analyzing data for the 80 percent of participants not taking a GLP-1 allowed the researchers to factor in diabetes severity.
The researchers found that when participants took semaglutide, they saw the following improvements:
- 42 percent lower risk of psychiatric-related hospital care and sick leave
- 44 percent lower risk of worsening or new depression
- 38 percent lower risk of worsening or new anxiety
- 47 percent lower risk of substance use disorder diagnosis or treatment
Other GLP-1 drugs showed more variable effects: Liraglutide was linked to a lower risk of worsening depression but not anxiety. Exenatide and dulaglutide showed no significant impact on mental health outcomes.
GLP-1 drugs as a whole were associated with a reduced risk of self-harm and substance use disorder.
These findings are “very robust and compelling,” says Jorge Moreno, MD, assistant professor and obesity medicine doctor at Yale Medicine in New Haven, Connecticut, who was not involved in the study.
“There have been some prior studies that show favorable mental health outcomes for patients on GLP-1, and this study builds a stronger case for mental benefits of specific GLP-1s,” says Dr. Moreno.
Although there have been concerns in the past that GLP-1 use may increase the risk of suicidal thinking, this study does not find evidence to support such a link, says coauthor Mark Taylor, MD, a professor at Griffith University School of Medicine in Southport, Queensland, Australia.
“Not only were depression and anxiety improved with some of these medications, they actually seem to help suicidality,” he says.
Why Semaglutide Stood Out
It’s not clear why the link to mental health benefits was stronger for semaglutide, says Dan Azagury, MD, a weight loss physician and bariatric surgeon at Stanford Medicine in California.
Compared with the other GLP-1s in this study, semaglutide is a newer drug and linked with greater weight loss, Dr. Azagury says, adding that more research is needed to confirm any link to mental health.
Semaglutide also has a longer half-life than the older GLP-1s and may have a stronger effect on receptors in the brain, which could help explain the difference in findings, Moreno adds.
How Might GLP-1s Improve Mood?
Although the reasons behind the link are unclear, experts believe it’s likely a combination of factors.
The potential protective effects of semaglutide on mental health could be due to weight loss, a decrease in “food noise,” some combination of the two, or an entirely different mechanism, perhaps related to GLP-1’s direct effects on the brain, says Anna Lembke, MD, a psychiatry professor at Stanford Medicine in California.
“Future studies should try to tease this apart,” says Dr. Lembke, who wasn’t involved in the research.
Some of the benefits may also be tied to physical health changes. “As diabetes improves and weight decreases, people often have more energy, sleep better, and feel physically better overall,” says Leslie J. Heinberg, PhD, vice chair of psychology in the Center for Behavioral Health at Cleveland Clinic in Ohio.
The Study Has Some Limitations
The study design — comparing people to themselves over time — helps reduce some variables among participants that can make findings inconclusive, says Dr. Heinberg, who wasn’t involved in the study.
But because this was an observational study, rather than a controlled intervention, researchers weren’t able to track important factors like weight loss, symptom severity, or lifestyle changes.
That makes it impossible to determine whether the medications themselves are driving the improvements or whether those changes are happening because of downstream effects, such as weight loss, better blood sugar control, or changes in daily life.
“It’s also important to note that these findings were done in a Swedish population with a national healthcare system. Further research needs to be done to include other people of other countries and ethnicities,” says Moreno.
Weight Loss Can Help Make Daily Activities More Comfortable
“Most of my patients are pretty pleased with how the [GLP-1] medication and weight loss has impacted their lives,” says Sherry Pagoto, PhD, a licensed clinical psychologist, researcher, and professor at the University of Connecticut in Storrs.
“People with obesity experience an invisible daily battle with appetite, not to mention weight stigma. To be freed from these things releases them from a huge burden,” says Dr. Pagoto.
When Pagoto asks her patients why they want to lose weight, “the most common answers always point to the desire to feel more comfortable doing everyday activities like play with their kids or grandkids, ride a rollercoaster, play a recreational sport, and so on,” she says.
“My patients would say that the extra pounds combined with low physical stamina stood in the way of activities they really enjoyed with family and friends. I suspect that because GLP-1 medications are so effective at helping people lose significant weight, patients are able to do more things they enjoy in life and without feeling tired, worn out, or embarrassed,” says Pagoto.
This would have a tremendous impact on mood. “Depression so often occurs because we disengage from activities that give us life satisfaction,” Pagoda says. “When people are able to do more of those things again, it can feel like a new lease on life.”
Mental Health Effects Aren’t the Same for Everyone
Experts emphasize that mental health responses to GLP-1 drugs can vary, so it’s important to keep your doctor or treatment provider informed of any mood changes.
Although many people see mood improvements on GLP-1s, others may struggle and find aspects of their lives not as rewarding or enticing as before, says Heinberg. “For example, some patients report a reduction in their libido or less enjoyment in activities due to the blunting of reward. For those who have an anhedonia component to their depression, they may find a worsening experience,” she says.
Anhedonia refers to a reduced ability to feel pleasure or interest in activities that are usually enjoyable.
Feeling down or ”off” after starting a GLP-1 could be due to uncomfortable GI side effects or frustration if weight loss is slower than expected, says Pagoto.
Expectations matter, too. People who go on GLP-1s thinking that weight loss is the solution to all of life’s problems are likely to be disappointed, she says.
“Weight loss won’t fix a failing relationship, work stress, family problems, or other aspects of life that are stressful,” says Pagoto.
Going into GLP-1 therapy with the assumption that weight loss is the only path to happiness is likely to be a setup for disappointment, she says.