Reminders on antipsychotic drug-induced disruptions in glucose homeostasis

Antipsychotic drug-induced changes in glucose homeostasis are often attributed to antipsychotic-induced weight gain. However, changes in glucose control can occur independently of weight gain. A recent systematic review and meta-analysis examined the association between antipsychotic use and glucose homeostasis, with consideration given to weight gain propensity, medication type and treatment duration.The analysis included blinded randomized clinical trials comparing changes in glucose homeostasis–related parameters between patients with severe mental illness or healthy volunteers assigned to antipsychotics or control (placebo or no intervention) groups. A total of 127 randomized controlled trials were included in the meta-analysis.The primary study outcomes were changes in fasting glucose, fasting insulin and glycated hemoglobin (A1C) following antipsychotic treatment. Secondary outcomes included any other glucose metabolism-related parameters (e.g., insulin resistance, hyperglycemia).Results showed the following:A total of 35,952 antipsychotic-treated patients and 19,010 placebo-treated patients were included in the qualitative synthesis.A total of 28,975 antipsychotic-treated and 15,101 placebo-treated patients were included in the meta-analysis.Antipsychotic use was associated with significantly increased fasting glucose, fasting insulin, A1C and hyperglycemia compared with placebo. Findings were corroborated in healthy volunteers.Subgroup analyses suggested that antipsychotic type (low, moderate or high risk of weight gain), diagnosis, age, concomitant medication use and previous antipsychotic exposure did not consistently affect dysglycemia risk.In meta-regression analyses, antipsychotic-associated dysregulations in glucose homeostasis were independent of study duration and antipsychotic dose.The authors note that to their knowledge, this study represents the largest, most comprehensive systematic review to examine disruptions in glycemic control associated with antipsychotic use. They conclude that antipsychotic exposure significantly disrupts glucose homeostasis independent of exposure duration, dose, diagnosis and propensity of the antipsychotic to cause weight gain. The authors recognize that although antipsychotic-induced weight gain contributes to glucose homeostasis dysregulation, there may also be weight gain-independent glycemic effects, which require further study. The authors stress that increased awareness of antipsychotic-induced dysregulation in glucose homeostasis is warranted. Ongoing metabolic monitoring is required as there appears to be no significant association between duration of antipsychotic use and antipsychotic-related disruptions in glycemic control.Reference:Smith ECC, Agarwal SM, Panganiban KJ, et al. Antipsychotic drugs and dysregulated glucose homeostasis. A systematic review and meta-analysis. JAMA Psychiatry 2025; Published online August 27, 2025. (accessed September 2, 2025).

Reminders on antipsychotic drug-induced disruptions in glucose homeostasis

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