The Potential Role of Antidiabetic Agents in Bipolar Disorder

This narrative review aims to summarize the evidence supporting the use of antidiabetic agents as potential adjunctive treatments in bipolar disorder (BD). The focus is on the shared pathophysiological mechanisms linking insulin resistance (IR) and BD, and on how metabolic modulation may influence mood, cognition, and treatment outcomes. Emerging research indicates that IR and related metabolic abnormalities are highly prevalent in BD and are associated with illness progression, cognitive impairment, and reduced treatment response. Studies involving metformin, pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists (such as liraglutide and semaglutide), and sodium–glucose cotransporter 2 (SGLT2) inhibitors (such as empagliflozin) have demonstrated improvements in depressive symptoms, metabolic parameters, and neuroinflammatory markers in individuals with mood disorders. Mechanistic evidence suggests that these agents may exert neuroprotective effects by enhancing insulin signaling, reducing oxidative stress, and improving mitochondrial and synaptic function. Nevertheless, the available studies are limited by small sample sizes and short follow-up durations. Targeting IR represents a promising translational approach for improving both metabolic and psychiatric outcomes in BD. Future research should prioritize mechanistic studies and randomized controlled trials designed to clarify optimal dosing, treatment duration, and patient selection, as bridging psychiatry and endocrinology through metabolic interventions could redefine treatment paradigms for bipolar disorder.