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Background: Atypical antipsychotics are the main treatment for a large number of psychiatric illnesses, with fewer extrapyramidal effects than conventional antipsychotics. However, it has been suggested that their use is associated with increased risk of dyslipidemia and type 2 diabetes mellitus., Objective: The risk of metabolic adverse effects associated with asenapine was assessed in comparison with that associated with olanzapine using real-world data., Methods: This study was a retrospective analysis based on data extracted from the Italian and Spanish Cegedim Strategic Data Longitudinal Patient-Data databases. Patients with asenapine or olanzapine prescriptions were retrieved from September 2010 to December 2012 using strict inclusion criteria to guarantee minimization of confounders. Patients with type 2 diabetes mellitus and dyslipidemia were identified by using ICD9 codes and by antidiabetic and dyslipidemic drug prescriptions. The presence or absence of the metabolic condition was compared before and after treatment, and between cohorts., Results: The retrospective analysis showed a lower risk of developing type 2 diabetes with asenapine than with olanzapine (2.2 vs 3.5%, respectively; p value: 0.0002) and of developing dyslipidemia (2.8 vs 6.8%, respectively; p value: 0.0001)., Conclusions: Asenapine is associated with a lower risk of metabolic adverse effects than olanzapine, demonstrating its improved safety profile.