Weight-Loss Drugs Like Wegovy Now Linked to Lower Depression Risk

Researchers examined 3,081,254 diabetic patients and 929,174 non-diabetic patients. They analyzed the association between GLP-1 medications and depression diagnosis after starting the medication.

Diabetic patients who were given any of the GLP-1 medications, aside from liraglutide, showed a lower incidence of depression compared to those who were not given the GLP-1 medication.

Researchers have been investigating if GLP-1 drugs are linked to increased risk of mental health issues. The Wegovy medication lists depression as a potential side effect and the FDA has investigated the issue but found no evidence of causation.

Tirzepatide demonstrated the most significant decrease in developing depression among diabetic patients. The non-diabetic patients who took semaglutide had a reduced risk of depression compared to those not prescribed the GLP-1 drug.

“This is an interesting study that provides foundational data for future studies,” said David Creel, Ph.D., psychologist with Cleveland Clinic’s Endocrinology and Metabolism Institute. “One strength of the study is that the sample size is very large and includes data from all 50 states, and over 1,300 hospitals.”

However, since the study is retrospective and lacks many of the controls of a randomized controlled trial, it’s important to be careful about drawing conclusions.

“Much of the data presented is correlational, which tells us there is a relationship between taking this class of medication and a reduced risk of depression/anxiety in people with diabetes and obesity,” Creel stated. “However, we cannot assume that the medications themselves are necessarily the reason for reduced risk. Although the research is promising, there are many factors that could potentially impact depression among people with obesity who are taking these medications (weight loss, physical activity, less medical burden, nutritional status, hopefulness, sleep, etc).”

Semaglutide and tirzepatide were the two medications most strongly related to decreased risk of depression and anxiety.

“These medications generally have the greatest impact on body weight,” said Creel. “It is possible that the impact on mood is mainly related to weight loss. It would be interesting to know if the people experiencing the most weight loss, independent of which medication was taken, had the least likelihood of developing depression.”

It is possible that the medications have a direct impact on mood as well as an indirect impact on mood through causing weight loss, Creel added.

“We know that there is a connection between obesity and depression, and it appears to be bi-directional. Obesity increases the risk of depression, and depression can increase the risk of weight gain,” he said.

There are certain mechanisms by which this class of medication might impact mood.

“People affected by depression can have neuroinflammation, neurotransmitter imbalances, and synaptic dysfunction,” Creel stated. “GLP-1 can reduce inflammation of nerves and may help protect against neurotransmitter imbalances.”

It may also help maintain synaptic function in the brain (the connection and communication between nerve cells). The degree to which these medications impact these mechanisms needs to be studied more, he explained.

“I think much of the depression and anxiety can be linked to the overwhelming feeling of helplessness patients experience when they are unable to achieve blood sugar and weight loss goals in a sustained fashion,” said Dr. Caroline Messer, endocrinologist at Northwell Lenox Hill Hospital.

“In addition, I commonly hear the sentiment that patients feel they are living in a body that is not theirs – almost akin to the gender dysmorphia often seen in my transgender population,” Messer stated. “The image staring back in the mirror doesn’t match the patient’s true identity.”

Experts say weight loss itself may lead to both social and physiological changes that impact mental health.

First, “Obesity is associated with inflammation and this inflammation may have direct, harmful effects on brain function,” said Creel.

Second, “What is indisputable is that people affected by obesity are often treated differently than people of normal weight. These biases can lead to a variety of mental health challenges including anxiety and depression.”

Also, some people with obesity become more isolated due to their weight and this social isolation can worsen mood. Obesity can make physical activity more difficult, and lack of physical activity is associated with increased depression and anxiety, Creel explained.

Depression can lead to unhealthy coping like emotional eating and unhealthy eating.

“One symptom of depression is low energy,” said Creel. “People with low energy may feel less likely to cook healthy meals, instead relying on calorie-dense convenience foods or fast foods. Research has demonstrated that intentional weight loss is often associated with improvements in mood.”

Obesity is associated with many conditions such as chronic pain, poor mobility, social stigma, increased utilization of medical services, and sleep disturbances.

With weight loss, these conditions tend to improve, leading to a better quality of life, Creel explained. This in turn can have a positive impact on mood. When obesity/diabetes treatments are working, the recipients of those treatments often feel a sense of control over their disease and this hope can be a powerful influence on their mood.

While further research is needed, researchers speculate that these drugs could serve a dual purpose: weight loss and treating anxiety and depression.

“Randomized controlled trials are needed to see if these medications are directly impacting mood or are mainly having an impact on mood through weight loss,” said Creel. “Many factors were not controlled for in this study (weight loss, nutritional factors, exercise level etc.). In addition, it is unknown how well depression was diagnosed.”

Also, many of the diagnostic criteria related to depression (lack of interest in activities, eating changes, sleep problems, feeling like a failure, and fatigue) are also associated with obesity or diabetes, he added.

Patients with diabetes who used GLP-1 drugs, including tirzepatide, semaglutide, dulaglutide, and exenatide had a decreased chance of being diagnosed with depression after starting the medication compared to those who did not take the drugs, according to a new study.

There was a lower likelihood of developing anxiety among diabetic patients for all GLP-1 medications that were investigated.

Experts say the improvement in mood may be due to the weight loss caused by these medications.