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Introduction The glucagon-like peptide-1 (GLP-1) receptor agonist drug class is widely prescribed to manage type 2 diabetes.1 In large trials of cardiovascular outcomes, GLP-1 receptor agonists were highly effective in achieving glycaemic control, showing beneficial cardiorenal effects and reducing all cause mortality.2 Despite these benefits, recent reports linking GLP-1 receptor agonists to suicidal ideation and self-harm have raised significant concerns.3 The initial signal regarding this possible safety problem emerged from the Icelandic Medicines Agency in July 2023, prompting regulatory bodies worldwide, including the European Medicines Agency and the US Food and Drug Administration, to launch independent investigations into the potential risk of suicidality among GLP-1 receptor agonist users.3 Despite these efforts, regulatory agencies have yet to reach definitive conclusions owing to limitations in the available evidence.45 Clinical trials of GLP-1 receptor agonists have not reported any imbalances in suicidal ideation or self-harm,67 whereas several observational studies have generated varied findings on of the effect of GLP-1 receptor agonists on the risk of suicidal ideation, self-harm, and suicide, which may be a result of methodological limitations in these studies.8910111213 From a biological standpoint, GLP-1 receptor agonists may lead to suicidality through different mechanisms, including hyperactivity of the hypothalamic-pituitary-adrenal axis,14 sudden weight loss leading to elevated suicide risk,1516 and under-expression of brain derived neurotrophic factor linking low body weight and increased anxiety, potentially contributing to higher suicidality.1718 However, the exact manner in which GLP-1 receptor agonists could increase the risk of suicidal ideation and self-harm remains unclear

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5.3 Mechanisms underlying the association between GLP-1RAs and AF A study has demonstrated that patients receiving GLP-1RA therapy exhibit a sustained increase in heart rate (146)

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