Skip to main content
SpringerLink
Log in

Managing glucose-related adverse events of antipsychotics is worth the effort

  • Drug Reactions and Interactions
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

Second-generation antipsychotics (SGAs) are first-line treatments for schizophrenia, bipolar disorder and severe depressive disorder, which together affect at least 10% of people. Most SGAs, but especially clozapine and olanzapine, can cause significant metabolic adverse events such as weight gain and diabetes, which are already more prevalent in psychiatric patients. Recommended options include carefully switching to an SGA with a better metabolic profile and adding metformin or weight loss drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists and North American Association for the Study of Obesity. Consensus Development Conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.

  2. Holt RIG. Association between antipsychotic medication use and diabetes. Curr Diab Rep. 2019;19(10):96.

    Article  Google Scholar 

  3. Cernea S, Dima L, Correll CU, et al. Pharmacological management of glucose dysregulation in patients treated with second-generation antipsychotics. Drugs. 2020;80(17):1763–81.

    Article  CAS  Google Scholar 

  4. Marvanova M. Strategies for prevention and management of second generation antipsychotic-induced metabolic side effects. Mental Health Clinician. 2013;3(3):154–61.

    Article  Google Scholar 

  5. Silvestre JS, Prous J. Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes. Methods Findi Exp Clin Pharmacol. 2005;27(5):289–304.

    Article  CAS  Google Scholar 

  6. Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64–77.

    Article  Google Scholar 

  7. Mizuno Y, Suzuki T, Nakagawa A, et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014;40(6):1385–403.

    Article  Google Scholar 

  8. Chen J, Huang XF, Shao R, et al. Molecular mechanisms of antipsychotic drug-induced diabetes. Front Neurosci. 2017;11:643.

    Article  Google Scholar 

  9. Holt RI, Hind D, Gossage-Worrall R, et al. Structured lifestyle education to support weight loss for people with schizophrenia, schizoaffective disorder and first episode psychosis: the STEPWISE RCT. Health Technol Assess. 2018;22(65):1–160.

    Article  Google Scholar 

  10. Teasdale SB, Ward PB, Samaras K, et al. Dietary intake of people with severe mental illness: systematic review and meta-analysis. Br J Psychiatry. 2019;214(5):251–9.

    Article  Google Scholar 

  11. Grajales D, Ferreira V, Valverde ÁM. Second-generation antipsychotics and dysregulation of glucose metabolism: beyond weight gain. Cells. 2019;8(11):1336.

    Article  CAS  Google Scholar 

  12. Speyer H, Christian BNH, Birk M, et al. The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity. World Psychiatry. 2016;15(2):155–65.

    Article  Google Scholar 

  13. Skrede STI, Tanum L, Steen VM, Bramness Incident users of antipsychotic agents and future use of cholesterol-lowering drugs: an observational, pharmacoepidemiologic study. J Clin Psychiatry. 76(1):e111-6.

  14. Correll CU, Sikich L, Reeves G, et al. Metformin add-on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial. World Psychiatry. 2020;19(1):69–80.

    Article  Google Scholar 

  15. Newcomer JW, Campos JA, Marcus RN, et al. A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine. J Clin Psychiatry. 2008;69(7):1046–56.

    Article  CAS  Google Scholar 

  16. Stroup TS, McEvoy JP, Ring KD, et al. A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry. 2011;168(9):947–56.

    Article  Google Scholar 

  17. Vancampfort D, Firth J, Correll CU, et al. The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019;18(1):53–66.

    Article  Google Scholar 

  18. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.

    Article  CAS  Google Scholar 

  19. Smith RC, Jin H, Li C, et al. Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: a randomized double-blind study. Schizophr Res. 2013;143(1):18–24.

    Article  Google Scholar 

  20. Siskind DJ, Leung J, Russell AW, et al. Metformin for clozapine associated obesity: a systematic review and meta-analysis. PLoS ONE. 2016;11(6):e0156208.

    Article  Google Scholar 

  21. Liu Z, Zheng W, Gao S, et al. Metformin for treatment of clozapine-induced weight gain in adult patients with schizophrenia: a meta-analysis. Shanghai Arch Psychiatry. 2015;27(6):331–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Praharaj SK, Jana AK, Goyal N, et al. Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis. Br J Clin Pharmacol. 2011;71(3):377–82.

    Article  CAS  Google Scholar 

  23. Silva VA, Suraweera C, Ratnatunga SS, et al. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16(1):341.

    Article  Google Scholar 

  24. Luo C, Wang X, Huang H, et al. Effect of metformin on antipsychotic-induced metabolic dysfunction: the potential role of gut-brain axis. Front Pharmacol. 2019;10:371.

    Article  CAS  Google Scholar 

  25. Out M, Kooy A, Lehert P, et al. Long-term treatment with metformin in type 2 diabetes and methylmalonic acid: post hoc analysis of a randomized controlled 4.3 year trial. J Diabetes Complicat. 2018;32(2):171–8.

    Article  Google Scholar 

  26. Ishøy PL, Knop FK, Broberg BV, et al. Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia: a randomized, placebo-controlled trial. Diabetes Obes Metab. 2017;19(2):162–71.

    Article  Google Scholar 

  27. Siskind D, Russell A, Gamble C, et al. Metabolic measures 12 months after a randomised controlled trial of treatment of clozapine associated obesity and diabetes with exenatide (CODEX). J Psychiatr Res. 2020;124:9–12.

    Article  Google Scholar 

  28. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–56.

    Article  CAS  Google Scholar 

  29. Larsen JR, Vedtofte L, Jakobsen MSL, et al. Effect of liraglutide treatment on prediabetes and overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia spectrum disorder: a randomized clinical trial. JAMA Psychiat. 2017;74(7):719–28.

    Article  Google Scholar 

  30. Siskind D, Hahn M, Correll CU, et al. Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: a systematic review and individual participant data meta-analysis. Diabetes Obes Metab. 2019;21(2):293–302.

    Article  CAS  Google Scholar 

  31. Thomopoulos C, Parati G, Zanchetti A. Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10—should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials. J Hypertens. 2017;35(5):922–44.

    Article  CAS  Google Scholar 

  32. Ryan DH, Yockey SR. Weight loss and improvement in comorbidity: differences at 5%, 10%, 15%, and over. Curr Obes Rep. 2017;6(2):187–94.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Caroline Fenton & Connie Kang

Authors
  1. Caroline Fenton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Connie Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Connie Kang.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Authorship

C. Fenton, a contracted employee of Adis International Ltd/Springer Nature, and C. Kang, a salaried employee of Adis International Ltd/Springer Nature, declare no relevant conflicts of interest.

Conflict of interest

All authors contributed to the review and are responsible for the article content.

Ethics approval Consent to participate, Consent for publication, Availability of data and material, Code availability

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fenton, C., Kang, C. Managing glucose-related adverse events of antipsychotics is worth the effort. Drugs Ther Perspect 37, 415–421 (2021). https://doi.org/10.1007/s40267-021-00856-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-021-00856-9

Search

Navigation