In the “South Park” special titled “The End of Obesity,” after Cartman takes Ozempic by injection, he experiences significant weight loss. This transformation is visually striking, showing Cartman in a much slimmer state than usual.
Cartman’s reaction to his new appearance is mixed. While he enjoys the attention and some immediate benefits, the episode satirizes the complexities and societal pressures associated with weight loss.
A new study from EMR software company Epic reports that five GLP-1 drugs were linked to reduced depression and anxiety in people with diabetes, compared with people who were not taking GLP-1 medications.
This group of medications is based on related compounds, all of which are glucagon-like peptide-1 (GLP) receptor agonists that mimic the natural GLP-1 intestinal hormone. In doing so, they produce insulin after eating, helping to reduce blood sugar. They also slow the emptying of the stomach and promote a sensation of being full, leading to a reduction in appetite.
The medications are generally injectable, although oral versions are also available.
The most well-known GLP-1 drugs, Wegovy and Ozempic, are based on semaglutide. Other GLP-1 agonist compounds tested in the study are liraglutide, dulaglutide, and exenatide, as well as tirzepatide that mimics a second intestinal hormone, gastric inhibitory polypeptide, or GIP, in addition to GLP-1.
People with diabetes taking tirzepatide were 65% less likely to be diagnosed with depression and 60% less likely to have anxiety, compared to people not taking GLP-1 drugs. People with diabetes who were taking semaglutide were 45% less likely to be diagnosed with depression, and 44% less likely to have anxiety.
Two of the drugs, semaglutide and liraglutide, were assessed as regards depression and anxiety in people without diabetes.
For people who do not have diabetes, only semaglutide was associated with a reduction in depression and anxiety, compared to people who were not on GLP-1 medications.
There was no statistically significant improvement for people taking liraglutide.
The study was undertaken by Epic Research, an investigative branch of Epic, one of the largest holders of electronic medical records in the U.S. Two teams of in-house researchers analyzed anonymized patient data, coming to the same conclusions.
The study analyzed patient records for 3,081,254 people with diabetes and 929,174 without diabetes, who were taking the drugs for weight loss. The researchers factored in a range of variables to eliminate confounding influences on their results.
Can Ozempic treat depression?
“The results suggest a potentially new therapeutic benefit of GLP-1 medications beyond their established use for glucose control and weight management,” said general practitioner with Zava, Dr. Kathryn Basford, who was not involved in the research.
Dr. Crystal Wyllie, also a general practitioner with Zava, who was also not involved in the research, noted that the study “goes some way in addressing concerns raised by the FDA [U.S. Federal Food and Drug Administration] about depression and suicidal ideation associated with semaglutide, as it suggests that these concerns may not be directly linked to these specific weight-loss treatments.”
In early January 2024, the FDA released an update regarding their investigation of a connection between GLP-1 drugs and suicidal ideation Trusted Source.
“Our preliminary evaluation has not found evidence that use of these medicines causes suicidal thoughts or actions,” the agency concluded.
Dr. Mir Ali, medical director at the MemorialCare Surgical Weight Loss Center, who was not involved in the study, was not surprised by the findings, saying, “There were only a few case reports and there’s hundreds of thousands of patients on these medications.”
One question left unanswered for now is whether the reduction in depression and anxiety diagnoses are a direct result of the medication.
Dr. Basford said the study “doesn’t definitively clarify whether these improvements are due to the biochemical effects of the medicines or are a result of improved self-esteem. I would be interested to see further research in this area.”
The impact of GLP-1 drugs on weight loss culture
With acknowledged benefits for people with diabetes, having first been approved for use in 2005, GLP-1 drugs for weight loss may re-position overweight and obesity in a clearly medical context, with the potential of reducing the historical stigma associated with these conditions.
“It’s a paradigm shift that we’re thinking of obesity not as a failure on the patient’s part to control their habits, but more of a chronic disease, and treating it like any other chronic disease such as diabetes or high blood pressure, arthritis, or other diseases that people readily will say is not the patient’s fault,” Dr. Ali said.
“My hope is that these treatments will allow patients to live healthier, happier lives — whatever weight they finally achieve,” said Dr. Wyllie.
“We need to recognize obesity as a multifaceted condition that requires interventions that address both the physical and psychological needs of the patient,” Dr. Basford added.
Off-label uses for GLP-1 drugs
Of the 13 GLP-1 medications listed by the FDA, only three, Wegovy (semaglutide), Saxenda (liraglutide), and Zepbound, (tirzepatide), are officially listed as approved for weight loss. However, they are commonly prescribed “off-label” for this purpose.
Dr. Ali explained that the lack of official approvals in this case may be less than they seem. “That’s just a drug company strategy for getting a broader indication for these medications — rebranding them and marketing them for weight loss.”
The cost of a GLP-1 medication may be intimidating in that one needs to remain on the drug long-term to maintain its effect for diabetes, weight loss, or perhaps a reduction in depression and anxiety.
Dr. Ali noted that “It is difficult to get it covered by most insurance companies,” but said many will pick up the tab if the individual meets medical qualifications. For weight loss, for example, one needs a Body Mass Index of 30 or above to obtain coverage from some insurance carriers.
- Improved Self-Esteem and Body Image:
- Weight loss can lead to improved self-esteem and body image, which may positively impact mental health. Patients who successfully lose weight often report feeling better about their appearance and overall health, which can reduce symptoms of anxiety and depression.
- Reduction in Anxiety and Depression:
- Some patients have reported reductions in anxiety and depression symptoms after losing weight with the help of Ozempic. This could be due to the physical benefits of weight loss, improved self-esteem, and better overall health.
- Enhanced Quality of Life:
- Weight loss can lead to increased physical activity, better sleep, and improved energy levels. These physical health improvements can contribute to a better quality of life and potentially enhance mental well-being.
- Direct Effects on Brain Chemistry:
- There is ongoing research into whether GLP-1 receptor agonists (the class of drugs to which Ozempic belongs) have direct effects on brain chemistry that could influence mood and cognition. Some studies suggest potential neuroprotective effects, but more research is needed to establish these benefits conclusively.
Anyone considering semaglutide for its mental health benefits should discuss this with their healthcare provider to weigh the pros and cons and to ensure it aligns with their overall treatment plan. Additionally, mental health improvements can vary widely among individuals, and not everyone may experience these benefits.
