U.S. Department of Veterans Affairs Health Services Research and Development Service.

Patients with schizophrenia are at increased risk for developing the metabolic syndrome or its individual components due to their lifestyle, suspected genetic predisposition, and exposure to antipsychotic medications that can cause weight gain and other metabolic side effects. Despite the availability of clinical guidelines, screening for and monitoring of metabolic problems in this patient population continue to be suboptimal. We provide an overview specifically addressing 1) why patients with schizophrenia are at increased risk for metabolic problems; 2) how commonly used antipsychotic medications vary in terms of their metabolic liability; 3) how to effectively screen for and monitor metabolic problems in patients receiving antipsychotic medications; 4) what interventions can prevent, limit, or reverse the metabolic side effects of antipsychotic drug treatment; and 5) what are the barriers to the care of these patients.

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Individuals receiving certain atypical antipsychotic medications are at risk of gaining weight and developing metabolic problems. There are no established drug treatments to prevent or counter these problems. However, the antihyperglycaemic agent metformin appears promising in some recent studies and we review the literature that evaluates metformin for limiting or reversing atypical antipsychotic drug-induced weight gain and glucose metabolism dysregulation. These studies suggest that metformin is beneficial if started early in antipsychotic drug treatment. Metformin has also been shown to prevent or delay the onset of type 2 diabetes mellitus in high-risk individuals from the general population. Based on these findings, we identify antipsychotic drug-treated patients who might benefit from metformin therapy and offer clinical guidelines for its use. Further long-term studies are needed to extend our observations and improve this strategy.

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Antipsychotic drug-induced weight gain and glucose dysregulation add to the cardiovascular risk of patients with schizophrenia and contribute to their early mortality. The currently recommended interventions to address the metabolic complications of antipsychotic drug treatment are to switch the patient from an antipsychotic drug with high metabolic liability to one with a lower liability and to implement lifestyle changes. These interventions can be quite challenging to carry out. So far the progress in improving the metabolic and cardiovascular outcome of patients with major mental illness has been disappointing. We offer an overview of the literature on metformin for antipsychotic drug-induced weight gain and glucose dysregulation and pertinent literature from the Diabetes Prevention Program. We conclude that young adults with schizophrenia newly exposed to antipsychotic drugs, who show a pattern of rapid weight gain and/or glucose dysregulation, are prime candidates for metformin if switching the antipsychotic medication to one with a lower metabolic burden is not an option or does not curtail the weight gain and/or adverse metabolic effects. Metformin therapy should not preclude healthy lifestyle interventions.

Background Persistent poorly-controlled type 2 diabetes mellitus (PPDM), or maintenance of a hemoglobin A1c (HbA1c) ≥8.5% despite receiving clinic-based diabetes care, contributes disproportionately to the national diabetes burden. Comprehensive telehealth interventions may help ameliorate PPDM, but existing approaches have rarely been designed with clinical implementation in mind, limiting use in routine practice. We describe a study testing a novel telehealth intervention that comprehensively targets clinic-refractory PPDM, and was explicitly developed for practical delivery using existing Veterans Health Administration (VHA) clinical infrastructure. Methods Practical Telehealth to Improve Control and Engagement for Patients with Clinic-Refractory Diabetes Mellitus (PRACTICE-DM) is an ongoing randomized controlled trial comparing two 12-month interventions: 1) standard VHA Home Telehealth (HT) telemonitoring/care coordination; or 2) the PRACTICE-DM intervention, a comprehensive HT-delivered intervention combining telemonitoring, self-management support, diet/activity support, medication management, and depression management. The primary outcome is HbA1c. Secondary outcomes include diabetes distress, self-care, self-efficacy, weight, depressive symptoms, implementation barriers/facilitators, and costs. We hypothesize that the PRACTICE-DM intervention will reduce HbA1c by >0.6% versus standard HT over 12 months. Results Enrollment for this ongoing trial concluded in January 2020; 200 patients were randomized (99 to standard HT and 101 to the PRACTICE-DM intervention). The cohort has a mean age of 58 and is 23% female and 72% African American. Mean baseline HbA1c and BMI were 10.2% and 34.8 kg/m 2 . Conclusions Because it comprehensively targets factors underlying PPDM using existing clinical infrastructure, the PRACTICE-DM intervention may be well suited to lower the complications and costs of PPDM in routine practice.