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Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics

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Abstract

Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A  systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium–glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.

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Authors and Affiliations

  1. Faculty of Medicine/Department M4/Internal Medicine IV, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Târgu Mureș, Romania

    Simona Cernea

  2. Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş, Romania

    Simona Cernea

  3. Department of Fundamental Disciplines and Clinical Prevention, Faculty of Medicine, Universitatea Transilvania, Nicolae Balcescu Str 59, Brașov, 500019, Romania

    Lorena Dima

  4. Charite Universitaetsmedizin, Department of Child and Adolescent Psychiatry, Berlin, and Campus Virchow-Klinikum, Mittelallee 5A, Berlin, 13353, Germany

    Christoph U. Correll

  5. Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Christoph U. Correll

  6. Department of Psychiatry and Molecular Medicine, Zucker Hillside Hospital, Northwell Health System, Glen Oaks, NY, USA

    Christoph U. Correll

  7. Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA

    Peter Manu

  8. Department of Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA

    Peter Manu

  9. South Oaks Hospital, Northwell Health System, Amityville, NY, USA

    Peter Manu

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Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Acadia Pharmaceuticals Inc., Alkermes, Allergan, Angelini Pharma, Axsome Therapeutics Inc., Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies Inc., Janssen Pharmaceuticals, Inc./Johnson & Johnson, LB Pharma, Lundbeck, MedAvante-ProPhase Inc., Medscape, Neurocrine Biosciences, Noven Pharmaceuticals Inc., Otsuka Pharmaceutical Co., Pfizer Inc., Recordati, Rovi, Sumitomo Dainippon Pharma, Sunovion Pharmaceuticals Inc., Supernus Pharmaceuticals Inc., Takeda Pharmaceutical Co., and Teva Pharmaceutical Industries Ltd. He has provided expert testimony for Janssen Pharmaceuticals, Inc. and Otsuka Pharmaceutical Co. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus Pharmaceuticals Inc, and Teva Pharmaceutical Industries Ltd. He received royalties from UpToDate and grant support from Janssen Pharmaceuticals, Inc. and Takeda Pharmaceutical Co. He is also a stock option holder of LB Pharma. Dr Cernea received payment for lectures from AstraZeneca, Boehringer Ingelheim, Berlin-Chemie Menarini, Eli Lilly, MSD, Novo Nordisk, Sanofi, Servier Pharma, for clinical trial Steering Committee meetings as National Lead Investigator for DECLARE-TIMI58 from TIMI Study Group, consultant fees for Advisory Board from AstraZeneca and support for travel to meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Sanofi, MSD, Novo Nordisk, Worwag Pharma. Drs Dima and Manu have nothing to declare.

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Cernea, S., Dima, L., Correll, C.U. et al. Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics. Drugs 80, 1763–1781 (2020). https://doi.org/10.1007/s40265-020-01393-x

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