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An increased activity of the hypothalamic-pituitary adrenal axis has been observed in patients with type 2 diabetes mellitus with asymptomatic autonomic imbalance with prevalent parasympathetic failure (20)
These include short-acting agents (e.g., exenatide BID), long-acting formulations (e.g., liraglutide, semaglutide, dulaglutide), dual agonists such as tirzepatide (GIP/GLP-1 RA), and novel oral agents like orforglipron and danuglipron
A 2025 meta-analysis in JAMA Psychiatry found no increase in depression or suicidality with GLP-1 medications versus placebo
These findings reveal a new role for natural gut GLP-1: it doesn't boost insulin release but instead sends a signal through gut nerves to make the body more responsive to insulin
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