Mental health outcomes / corollaries of nutritional interventions vs use of GLP-1 pharmaceuticals

What is a GLP-1?

Glucagon-Like-Peptide-1 Receptor Antagonists, or GLP-1s are medications used to treat type 2 diabetes and obesity. These medications are used to improve glycemic efficacy, reduce weight and blood pressure, improve chances of eliminating cardiovascular disease, and do not cause hypoglycemia (low blood sugar).[1] There are seven types of GLP-1s with semaglutide and liraglutide being the most common; many of these are injection form.  

Currently there are only 2 FDA approved GLP-1s for weight loss, Wegovy (semaglutide), and Saxenda (liraglutide). Wegovy just got its FDA approval in 2021. There has been discussion of approving Ozempic for weight loss, but the interesting thing is that Ozempic and Wegovy are the same medication called semaglutide. The reason it is sold under two different names is because they do not contain the same amount of medication.[2]  

When are GLP-1s prescribed?

GLP-1s are typically not recommended to be used as the first method in treating type 2 diabetes or obesity. For type 2 diabetes, healthcare professionals will prescribe a GLP-1 if a patient is not responding to the first treatment, metformin, and is unable to reach their glycemic goal. They will also prescribe a GLP-1 if a patients’ HbA1c is 1.5% higher above their target.[3] For obesity, there is not a uniform process for obtaining a prescription for a GLP-1, typically a healthcare professional will look at BMI and other lab work to determine the best course of action. 

Recently, there have been an increasing number of reports of GLP-1s not working in people using the medication for weight loss. A person is determined as a “Nonresponder” if a person does not lose 5% of their body weight within 90 days.[4] Doctors are still looking into possible reasons for this but have theorized that genetics, interactions with other medications, and other medical conditions could explain why some people do not respond.[5] 

Only a small percentage (4%) of Americans are on GLP-1 medications, although lately, we hear a lot about these medications on the news. Some theorize that as more and more adults get put on GLP-1s it could affect certain food industries like the snacking industry.[6]

The effects of GLP-1s on mental health

There are conflicting reports on whether GLP-1s have a positive or negative effect on an individual’s mental health status.

Some reports have shown that liraglutide and semaglutide have an associated risk of increasing depression, suicidal thoughts, and self-injury.[7] Preexisting mental health conditions make it difficult to say with certainty if GLP-1s are directly related to poor mental health outcomes.[8] Multiple physicians have theorized that preexisting mental health conditions in obese patients trying to lose weight may be an example of reverse causality. The people who may have depression due to their obesity will look for some sort of weight loss intervention and if the treatment does not work there is a higher risk of suicidal thoughts or self harm.[9] 

The process of actually getting the medication can also create mental stress. Many insurances do not cover medications specifically used for weight loss, using a coupon code from Goodrx, a month's supply of Wegovy is $1,300, and Ozempic is just under $1,000. There are also shortages of these medications due to the influx of people taking them, which also contributes to the increasing prices of the medications.[10] The increase in sales is most likely due to the medications being approved for both weight loss and type 2 diabetes. Patients using the medications for weight loss do not need to go through metformin first. There are some unpleasant side effects of GLP-1s, mostly gastrointestinal. Recent findings have revealed another possible side effect: reduced effectiveness of birth control. The specific reasons for this are still being looked into, but it may be because the weight loss from the medication is leading to a more regular menstrual cycle.[11] Since there are a high number of side effects that come with GLP-1s, taking an alternate route to lose weight may present better mental health and well-being outcomes.                            

There are a few different reasons why some scientists theorize why GLP-1s can improve mental health. A meta-analysis done in 2022 reported a significant change in baseline depression scores in patients taking GLP-1s.[12] Even though these medications may act as an antidepressant in some cases, it is not supposed to replace an actual antidepressant. Another theory on GLP-1s showing positive mental health effects is on the “gut-brain axis” and improved memory function. Scientists are just starting to understand how our microbiomes and mental health are connected.The gut-brain axis interacts with other organs, including the brain, so an impaired gut-brain-axis-metabolism is common in people with depression.[13] This has to do with neuroinflammation, and GLP-1 is thought to lower this inflammation response, improving the gut-brain axis, and easing the symptoms of depression.[14] Depression is also linked with memory loss, and GLP-1s may have the ability to enhance memory, although this is still being researched.[15]

Since these medications are only a temporary fix, a person may expect to lose weight, get off of the medication and continue life without making any changes, but this most likely will not work. It has been proven that after discontinuation of weight loss medications, a person may end up gaining back the weight. This will most likely impact someones’ mental health in a negative manner. A study published in April 2022 tested to see the average weight gain after discontinuation of semaglutide. The subjects used weekly semaglutide injections for 68 weeks, had a BMI of greater than or equal to 20, and received a “lifestyle intervention”.[16] Each participant had an average weight loss of 17.3% of their body weight with the medication (from weeks 0-68). After a year without the medication, the participants gained back ⅔ of their weight demonstrating that ongoing treatment could be necessary for weight management without lifestyle and behavioral change.[17]

Nutritional intervention

The Centers for Disease Control and Prevention (CDC) defines medical nutrition therapy as a nutrition-based treatment provided by a registered dietitian nutritionist, and includes a nutrition diagnosis as well as therapeutic and counseling services to help manage diabetes and obesity.[18]

Increasing efforts to nutritional therapy are usually the first steps in treating obesity because changing diet is the least invasive way to treat the condition. When nutritional intervention is used in early cases of obesity or type 2 diabetes it has the potential to eliminate pharmaceuticals completely, saving individuals and the healthcare system thousands of dollars. 

Nutritional therapy may have the ability to relieve symptoms of depression. The American Psychiatric Association (APA) directed a poll in March 2023 in which a little over 2,000 adults responded to questions related to diet, mental health, and well-being. About 80% said they would be open to changing their diet in a way that was positive for mental health, and 43% said they would be very open to changing their diet and improving mental health.[19] This survey shows that people want what is best for their health, they just need the right tools and education to do so.

Poor nutrition can be associated with low mental health status, and when nutritional interventions are done correctly, it can benefit both physical and mental health. One of the reasons why processed or sugary foods could cause poor mental health is because of the inflammatory response that happens when we consume these foods. Inflammatory responses are related to depression symptoms.[20] One way to reduce inflammation is by adhering to the Mediterranean diet, which is high in fruits and vegetables, moderate in poultry, eggs, and dairy, and very limited in red meat.[21] If you do not want to stick to the Mediterranean diet, there are plenty of other anti-inflammatory foods and diets that a person can implement for better nutrition. 

Eating foods that are “good for the brain” such as leafy vegetables, berries, walnuts, and tea may also decrease risk of developing chronic conditions like type 2 diabetes, and cardiovascular disease.[22] Nutritional intervention has also been a treatment for some mental conditions such as ADHD, PTSD, depression, and bipolar disorder. [23 ]Not consuming the right amounts of micro and macronutrients puts us at risk for mental health conditions. For example, low levels of vitamin D have been linked to depression and schizophrenia.[24]

 Amounts in excess of $250 million have been spent on obesity downstream effects rather than directing efforts to address the underlying cause.[25] Focusing on possible sources of type 2 diabetes and obesity, such as inadequate nutrition is one of the ways we can eliminate these chronic conditions, and reduce the number of individuals who need treatment. As we improve physical health through nutrition it can also have a positive effect on mental health leading to overall higher well-being. 

Summary

 Obesity treatment and management of type 2 diabetes requires both an educational and behavioral component. Without these, a person solely relying on medication may struggle to achieve maintainable results. [26] It is important to remember that treatment of obesity and management of type 2 diabetes is not the same for everyone. The use of pharmaceuticals along with proper diet may be the answer for some people, but that may not be the case for everyone. Our diet can be a transformative factor and has the potential to reverse certain chronic conditions. It is just a matter of adhering to a healthy lifestyle.

References

1 Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151

2 Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151

3 Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151

4 The use of GLP-1 medications in weight loss. Teladoc Health Inc. . (n.d.). https://library.teladochealth.com/hc/en-us/articles/13541411192595-The-Use-of-GLP-1-Medications-in-Weight-Loss-

5 The use of GLP-1 medications in weight loss. Teladoc Health Inc. . (n.d.). https://library.teladochealth.com/hc/en-us/articles/13541411192595-The-Use-of-GLP-1-Medications-in-Weight-Loss-

6 Smith, M. (2024, April 18). Higher prices shifting snacking landscape. Food Business News. https://www.foodbusinessnews.net/articles/25918-higher-prices-shifting-snacking-landscape

7  Arillotta, D., Floresta, G., Guirguis, A., Corkery, J. M., Catalani, V., Martinotti, G., Sensi, S. L., & Schifano, F. (2023, October 24). GLP-1 receptor agonists and related mental health issues; insights from a range of social media platforms using a mixed-methods approach. MDPI. https://www.mdpi.com/2076-3425/13/11/1503

8  Arillotta, D., Floresta, G., Guirguis, A., Corkery, J. M., Catalani, V., Martinotti, G., Sensi, S. L., & Schifano, F. (2023, October 24). GLP-1 receptor agonists and related mental health issues; insights from a range of social media platforms using a mixed-methods approach. MDPI. https://www.mdpi.com/2076-3425/13/11/1503

9 O’Riordan, M. (2023, July 12). EMA investigating suicidal thinking with GLP-1 drugs for weight loss. TCTMD.com. https://www.tctmd.com/news/ema-investigating-suicidal-thinking-glp-1-drugs-weight-loss

10  Arillotta, D., Floresta, G., Guirguis, A., Corkery, J. M., Catalani, V., Martinotti, G., Sensi, S. L., & Schifano, F. (2023, October 24). GLP-1 receptor agonists and related mental health issues; insights from a range of social media platforms using a mixed-methods approach. MDPI. https://www.mdpi.com/2076-3425/13/11/1503

11 Herbert, O. (2024, March 22). OZEMPIC patients report higher fertility causing “ozempic babies.” The Independent. https://www.independent.co.uk/life-style/pregnant-women-ozempic-babies-b2517305.html

12 Chan, X., Zhao, P., Wang, W., Guo, L., & Pan, Q. (2023, August 21). The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. Redirecting. https://doi.org/10.1016/j.jagp.2023.08.010

13 Kim, Y. K., Kim, O. Y., & Song, J. (2020). Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function. Frontiers in pharmacology, 11, 1270. https://doi.org/10.3389/fphar.2020.01270

14 Kim, Y. K., Kim, O. Y., & Song, J. (2020). Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function. Frontiers in pharmacology, 11, 1270. https://doi.org/10.3389/fphar.2020.01270

15 Kim, Y. K., Kim, O. Y., & Song, J. (2020). Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function. Frontiers in pharmacology, 11, 1270. https://doi.org/10.3389/fphar.2020.0127

16 Wilding, J. P. H., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., Lingvay, I., McGowan, B. M., Oral, T. K., Rosenstock, J., Wadden, T. A., Wharton, S., Yokote, K., Kushner, R. F., & STEP 1 Study Group (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, obesity & metabolism, 24(8), 1553–1564. https://doi.org/10.1111/dom.14725

17 Wilding, J. P. H., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., Lingvay, I., McGowan, B. M., Oral, T. K., Rosenstock, J., Wadden, T. A., Wharton, S., Yokote, K., Kushner, R. F., & STEP 1 Study Group (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, obesity & metabolism, 24(8), 1553–1564. https://doi.org/10.1111/dom.14725

18 Centers for Disease Control and Prevention. (2023, July 21). Medical nutrition therapy. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/dsmes-toolkit/reimbursement/medical-nutrition-therapy.html

19 Staff, A. (2023, April 18). How to boost mental health through better nutrition. American Society for Nutrition. https://nutrition.org/how-to-boost-mental-health-through-better-nutrition/#:~:text=A%20healthy%20diet%20provides%20more,to%20reduce%20symptoms%20of%20depression.

20 Firth, J., Gangwisch, J. E., Borisini, A., Wootton, R. E., & Mayer, E. A. (2020). Food and mood: how do diet and nutrition affect mental wellbeing?. BMJ (Clinical research ed.), 369, m2382. https://doi.org/10.1136/bmj.m2382

21 Firth, J., Gangwisch, J. E., Borisini, A., Wootton, R. E., & Mayer, E. A. (2020). Food and mood: how do diet and nutrition affect mental wellbeing?. BMJ (Clinical research ed.), 369, m2382. https://doi.org/10.1136/bmj.m2382

22 Foods linked to better brainpower. Harvard Health. (2021, March 6). https://www.health.harvard.edu/healthbeat/foods-linked-to-better-brainpower

23 Lachance, L., & Ramsey, D. (2015). Food, mood, and brain health: implications for the modern clinician. Missouri medicine, 112(2), 111–115.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170050/

24 Grajek, M., Krupa-Kotara, K., Białek-Dratwa, A., Sobczyk, K., Grot, M., Kowalski, O., & Staśkiewicz, W. (2022). Nutrition and mental health: A review of current knowledge about the impact of diet on mental health. Frontiers in nutrition, 9, 943998. https://doi.org/10.3389/fnut.2022.943998

25 Murad, J. (2023, December 5). Obesity: How do we treat America’s silent killer without breaking the economy? MedicalEconomics. https://www.medicaleconomics.com/view/obesity-how-do-we-treat-america-s-silent-killer-without-breaking-the-economy-

26 Murad, J. (2023, December 5). Obesity: How do we treat America’s silent killer without breaking the economy? MedicalEconomics. https://www.medicaleconomics.com/view/obesity-how-do-we-treat-america-s-silent-killer-without-breaking-the-economy-