Association Between Dextromethorphan/Bupropion with Diabetes Mellitus and Hyperglycemia: Reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)

Abstract

IntroductionDextromethorphan/bupropion (DXM/BUP) is the first orally administered antidepressant approved by the United States Food and Drug Administration (U.S. FDA) that combines dextromethorphan (i.e., a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist) and bupropion (i.e., a CYP2D6 inhibitor and antidepressant).DXM/BUP was FDA-approved for the treatment of Major Depressive Disorder (MDD) in adults in August 2022.Select psychotropic agents prescribed for MDD are known to alter glucose and insulin homeostasis.Herein, we sought to determine, using pharmacovigilance data, whether disproportionate reporting of diabetes mellitus or hyperglycemia associated with DXM/BUP has occurred. Research Designs and MethodsThis exploratory report investigated the association between DXM/BUP and the reporting of metabolic adverse events (i.e., hyperglycemia and diabetes mellitus).Disproportionality analyses were conducted using reporting odds ratios (RORs), with DXM/BUP and comparator agents evaluated relative to a reference comparator (acetaminophen).Data were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) from year of approval to April 26, 2026.A sensitivity analysis was performed on a restricted dataset obtained from FAERS from January 1, 2022, to April 30, 2026.Statistical significance was defined as a 95% confidence interval (CI) excluding 1.0. Results DXM/BUP was not associated with disproportionate reporting of diabetes mellitus (ROR = 0.33, 95% CI [0.07, 1.65], p = 0.18) and hyperglycemia (ROR = 0.10, 95% CI [0.01, 1.67], p = 0.11)