Type 2 diabetes in youth exposed to antipsychotics: a systematic review, meta-analysis and exploratory metaregression analysis

Importance: Antipsychotics are used increasingly in youth for non-psychotic and off-label indications, but cardiometabolic adverse effects and, especially, type-2 diabetes (T2DM) risk have raised concern. Objective: To assess T2DM riskassociated withantipsychotic treatment in youth. Data Sources:Systematic literature search of PubMed and PsycInfo without language restrictions from database inception until 05/04/2015. Study Selection:Longitudinal studies reporting on T2DM incidence in ≥20 youth aged ≤24 yearsexposed to antipsychotics for ≥3 months. Data Extraction and Synthesis:Two independent investigators extracted study-level data for a random effects meta-analysis and meta-regression of T2DM risk. Main Outcome(s) and Measure(s): The co-primary outcomes were study-defined T2DM, expressed as (i) raw incidence, or (ii) incidence rate per patient-years. Secondary outcomes included the raw T2DM incidence and incidence rate per patient-years comparedtopsychiatric controls (PCs)not receiving antipsychotics or to healthy controls (HCs). Results:Among 13 meta-analyzed studies (n=185,105antipsychotic-exposed youth, patient years=310,438, age=14.1±2.1 years,males=59.5±8.0%, follow-up=1.7±2.3 years), 7 studies includedPCs (n=1,342,121; patient years=2,071,135) and8 included HCs(n=298,803; patient years=463,084).Antipsychotic-exposed youth had a raw T2DM incidenceof5.7/1,000 patients (95% confidence interval (CI)=3.5-9.1; p