GLP-1s associated with reduced risk for depression, anxiety in patients with diabetes
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Key takeaways:
- Tirzepatide was associated with the greatest reduced risk for both anxiety and depression diagnoses.
- Only semaglutide was associated with reduced depression and anxiety risk in patients without diabetes.
Patients with diabetes on one of several GLP-1 receptor agonists were less likely to be diagnosed with depression and anxiety compared with those not on those medications, researchers found.
“Our findings suggest that GLP-1 medications could potentially have a dual benefit for patients, not only in managing their diabetes or obesity but also in potentially reducing the likelihood of depression and anxiety diagnoses,” Kersten Bartelt, RN, a clinician at Epic Research, told Healio.
Mental health correlations with antiobesity medications have been a recent focus in research, with one study associating semaglutide (Wegovey/Ozempic, Novo Nordisk) with a lower risk for suicidal ideation.
In the current study, the researchers analyzed 3,081,254 patients with diabetes and 929,174 patients without diabetes, adjusting for patient sex, age and history of depression and anxiety.
In the cohort of patients without diabetes, those prescribed GLP-1 receptor agonists were compared with those who were taking other weight management drugs.
In the cohort of patients with diabetes, meanwhile, those prescribed GLP-1 receptor agonists were compared with randomly selected patients with HbA1c lab results following their diabetes diagnosis who were not taking GLP-1 receptor agonists.
The GLP-1 receptor agonists included the following:
- semaglutide;
- tirzepatide (Zepbound, Eli Lilly);
- dulaglutide (Trulicity, Eli Lilly);
- exenatide (Byetta, Eli Lilly); and
- liraglutide (Saxenda, Novo Nordisk).
Overall, patients with diabetes who were prescribed any of these medications, except for liraglutide, had a decreased risk for depression diagnoses. ORs were:
- 0.89 (95% CI, 0.85-0.92) for exenatide;
- 0.84 (95% CI, 0.83-0.85) for dulaglutide;
- 0.55 (95% CI, 0.54-0.56) for semaglutide; and
- 0.35 (95% CI, 0.33-0.36) for tirzepatide.
Meanwhile, all five medications were associated with a reduced risk for anxiety diagnoses in patients with diabetes, with ORs of:
- 0.87 (95% CI, 0.85-0.88) for liraglutide;
- 0.78 (95% CI, 0.76-0.79) for dulaglutide;
- 0.76 (95% CI, 0.73-0.79) for exenatide;
- 0.56 (95% CI, 0.55-0.56) for semaglutide; and
- 0.4 (95% CI, 0.38-0.42) for tirzepatide.
Among patients who did not have diabetes, only those prescribed semaglutide had a lower risk for anxiety (OR = 0.69; 95% CI, 0.68-0.71) and depression (OR = 0.63; 95% CI, 0.61-0.64) compared with those who were not prescribed the medication.
Although the findings showed reduced odds for depression and anxiety for many of the medications, “providers should still monitor for these, as well as other short-term and long-term side effects, for their patients on any GLP-1 medication,” according to Bartelt.
“Further investigation into whether these findings hold true for various subpopulations could expand the knowledge in this space, and future research should also consider if there are any long-term effects of GLP-1 medications on mental health,” she said.
Perspective
Back to TopJonathan Terry, DO, QME, DABPN, ABIHM
In reviewing this research, I find myself with more questions than answers. I wonder what criteria might have led a patient to be more likely to be prescribed a GLP-1 medication than not and if this led to any type of selection bias when looking at outcomes for depression and anxiety. I am curious if barriers to payment for a GLP-1 medication might predispose a patient to be more likely to develop depression or anxiety. Of the 233 million records analyzed, I wonder about geographic, socioeconomic, cultural, or other variations in the data. As a whole, although this is interesting, I am not yet convinced that the correlation signifies causation. In order to develop more firm conclusions, I would want further information on the study populations and accounting for as many variables as possible to ensure that the GLP-1 administration is the primary difference in the test groups.
Perspective
Back to Top
At face value, this review seems to affirm the FDA’s initial finding of no direct link between GLP-1 medications and increased depression symptoms and/or suicidal thoughts. In reviewing the study design, an adequate number of patients were reviewed, but it is not clear how the investigators “adjusted for patient age, sex and history of depression and anxiety” as noted. I also question the comparison of GLP-1 weight loss medications to non-GLP-1 weight loss medications because most of the medications in non-GLP-1 classes work to alter brain chemistry and would be much more likely to induce new or worsening symptoms of anxiety and depression. I did find it interesting that the medications with better outcomes data with respect to lowering HbA1C and weight loss showed less likelihood for the development of anxiety and depression. It would be interesting to see if this held true for patients without diabetes now that tirzepatide has been approved and formulated for weight loss as well.
Clinically, as a prescriber of a variety of the GLP-1 medications, I can say that many patients on these medications have prior diagnoses of anxiety and/or depression, and a vast majority of patients who have seen positive results from these medications would report improvement in their depression and anxiety symptoms. I suspect this improvement is multifactorial because diabetic patients feel better overall once their blood sugar is more adequately controlled, and obese patients find improved musculoskeletal symptoms and body image thoughts as they lose weight on these medications.
In my opinion, this study shows that there was not an increase in new diagnoses of depression and anxiety after starting a GLP-1 medication, but there is not sufficient evidence to argue that using these medications would decrease overall risk for developing depression or anxiety. I would welcome more studies on the overall effect of these medications on mental health and how it correlates to a whole-person approach to patient care.
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Most GLP-1 medications correlated with a lower likelihood of anxiety and depression diagnoses. https://www.epicresearch.org/articles/most-glp-1-medications-correlated-with-a-lower-likelihood-of-anxiety-and-depression-diagnoses. Published Feb. 6, 2024. Accessed Feb. 14, 2024.
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