Risk of Treatment-Emergent Diabetes Mellitus in Patients Receiving Antipsychotics

Abstract

Background: Type 2 diabetes mellitus has been reported during antipsychotic treatment. Objective: To quantify the potential risk of treatment-emergent diabetes mellitus among patients receiving antipsychotic medications. Methods: The MEDLINE and Psychinfo databases were searched using the key words antipsychotic (including individual drug names), diabetes, risk, and incidence for all English-language articles published between 1966 and 2005. Risk calculations were performed using data obtained from pharmacoepidemiologic studies that met the following criteria: (1) cohort design, (2) determination of preexisting diabetes, (3) inclusion of antipsychotic monotherapy as an exposure variable, and (4) comparison with exposure to first-generation antipsychotics. Studies meeting these criteria were used to calculate incidence, attributable risk between agents, and number needed to harm. Results: A total of 25 observational pharmacoepidemiologic studies were found comparing antipsychotics on the outcome of diabetes mellitus. Sufficient information was provided in 15 of the reports to be able to estimate attributable risk, Attributable risk for individual second-generation antipsychotics relative to first-generation antipsychotics ranged from 53 more to 46 fewer new cases of diabetes per 1000 patients. Little observable difference was noted between the individual second-generation antipsychotics versus first-generation antipsychotics on this outcome. However, few of the studies controlled for body weight, race or ethnicity, or the presence of diabetogenic medications. None adjusted for familial history of diabetes, levels of physical activity, or diet, as this information is not usually available in the databases used in pharmacoepidemiologic studies. Conclusions: Based on the published pharmacoepidemiologic reports reviewed, the avoidance of diabetes as an outcome cannot be predictably achieved with precision by choice of a second- versus a first-generation antipsychotic. Risk management for new-onset diabetes requires the assessment of established risk factors such as family history, advancing age, non-white ethnicity, diet, central obesity, and level of physical activity.