Daily patterns of opioid and stimulant use and associated risk-behavior outcomes: A cohort study.

Diabetes and its related complications represent one of the leading contributors to illness and death and place a significant financial burden on the health care system []. Globally, it is estimated that 529 million individuals, corresponding to approximately 6.1% of the age‐standardized population, are affected by diabetes, and its prevalence has nearly doubled over the past two decades []. Diabetes is known to be a chronic metabolic condition associated with an increased risk of cardiovascular complications, kidney disease, and premature mortality []. Glucagon‐like peptide‐1 receptor agonists (GLP1RAs) have been increasingly recommended for patients with type 2 diabetes, particularly those with cardiovascular or chronic kidney disease, due to their demonstrated benefits in glycemic control, weight reduction, and mitigation of diabetes‐related complications [, , , ]. However, recent safety concerns have emerged regarding the potential psychiatric effects of GLP1RAs []. In July 2023, the Icelandic Medicines Agency reported signals suggesting an association between GLP1RA therapy and suicidal ideation, prompting regulatory investigations by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) [, ]. Nevertheless, the psychiatric safety profile of GLP1RAs remains controversial due to inconsistent findings across previous studies []. While some pharmacovigilance studies found suicidality signals with GLP1RAs, especially liraglutide [, ], large‐scale observational studies and analyses of global pharmacovigilance databases have generally failed to support a causal relationship [, , , ]. Moreover, a recent meta‐analysis found no association between GLP1RA use and psychiatric outcomes; however, most included trials relied on placebo comparators rather than active treatments, limiting the interpretability of these findings in routine clinical practice []. These inconsistencies and methodological limitations highlight the need for additional real‐world evidence to clarify the psychiatric safety profile of GLP1RAs. Several biological mechanisms have been proposed to explain the potential link between GLP1RAs and neuropsychiatric outcomes, including dysregulation of the hypothalamic–pituitary–adrenal axis, rapid weight reduction leading to psychological stress, and alterations in neurotrophic signalling [, ]. Conversely, experimental evidence suggests that GLP‐1 signalling may exert neuroprotective and mood‐stabilizing effects, adding the complexity of interpreting clinical observations [, ].