Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study

Abstract

Background: Previous findings on using Glucagon-like peptide-1 receptor agonist (GLP1-RA) as an antidepressant were conflicting, lacking large-scale studies. We used population-based data to investigate depression and anxiety risk in diabetic patients receiving the medication.Methods: From claims records of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified cohorts of 10,690 GLP1-RA users and 42,766 propensity score-matched patients without GLP1-RA use from patients with diabetes mellitus (DM) diagnosed in 2011–2017, matched by age, gender, index year, occupation, urbanization, comorbidities, and medications. Incidence, hazard ratios (HR) and 95% confidence interval (CI) of depression and/or anxiety were estimated by the end of 2017.Results: The overall combined incidence of anxiety and/or depression was lower in GLP1-RA users than in non-users (6.80 versus 9.36 per 1,000 person-years), with an adjusted HR adjusted hazard ratio (aHR) of 0.8 (95% CI: 0.67–0.95) after controlling for covariates. The absolute incidence reduction was greater in anxiety (2.13 per 1,000 person-years) than in depression (0.41 per 1,000 person-years). The treatment effectiveness was significant for women. Patients taking GLP1-RA for longer than 180 days had the incidence of anxiety reduced to 2.93 per 1,000 person-years, with an aHR of 0.41 (95%CI: 0.27–0.61), compared to non-users. Dulaglutide could significantly decrease risks of both anxiety and depression.Conclusion: Patients with DM receiving GLP1-RA therapy have a greater reduction of the risk of anxiety than that of depression. Our findings strengthen previous research that advocated possible anti-depressant or anxiolytic effects of GLP1-RA and may lead to improved treatment adherence among patients with DM.

Liraglutide 3.0 mg and Mental Health: Can Psychiatric Symptoms Predict Adherence to Therapy? Insights from a clinical audit

“…This mechanism is effective in traditional antihyperglycemic agents, such as insulin or metformin, and the newer GLP-1 RAs [21]. Indeed, research has amply demonstrated that the use of GLP-1 RAs in T2DM patients is associated with a lower incidence of depression and anxiety compared to controls treated with different therapies [47,48,23]. In addition, recent studies evaluating the gut microbiota have suggested that one of the roles of GLP-1 RAs in treating anxiety is related to improved glucoregulation, leading to reduced proin ammatory cytokines and increased neuroprotection [49].…”

“…In addition to their metabolic effect, GLP-1 RAs have also shown relevant effects in mental health. In particular, an increasing amount of research focuses on GLP-1 RAs e cacy in reducing anxiety and depressive symptoms, highlighting an important connection between metabolic regulations and psychopathological mechanisms [20][21][22][23][24]. In fact, recent studies point out that disturbed homeostasis between the nervous system and the immune and endocrine systems, disturbances in cerebral energy metabolism, and dysfunction of the gut-brain axis could play an important role in the pathogenesis of depression and anxiety: GLP-1RAs, through a modulatory effect on the immune, endocrine, and metabolic processes in the central nervous system, appear to act actively in ameliorating these symptoms [20,25].…”

Liraglutide 3.0 mg and mental health: can psychiatric symptoms be associated to adherence to therapy? Insights from a clinical audit

“…Anti-hyperglycemic agents, such as metformin and GLP-1 RAs, have consistently shown to exert anti-depressive properties [ 21 ]. Indeed, there is wide evidence that the use of GLP-1 RAs in T2DM patients is associated with a lower incidence of depression and anxiety compared to controls treated with different therapies [ 23 , 48 , 49 ]. In addition, recent studies evaluating the gut microbiota have suggested that one of the roles of GLP-1 RAs in treating anxiety is related to improved glucoregulation, leading to reduced proinflammatory cytokines and increased neuroprotection [ 50 ].…”

Question

“…In a 2019 meta-analysis of 8 RCTs of individuals receiving GLP-1 agonists, GLP-1 agonists were associated with greater reduction in depressive symptoms compared with control treatments 8 . In a study using claim records from the National Health Insurance Research Database of Taiwan, 10,690 GLP-1 RA users were compared with 42,766 non-users matched by age, gender, index year, occupation, urbanization, comorbidities, and medications 9,10 . Compared with individuals not using GLP-1 RAs, those using GLP-1 RAs had a significantly reduced risk of anxiety and a moderate reduction of depression.…”