References:1. Whicher CA, Price HC, Holt RIG, et al. Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation. Eur J Endocrinol. 2018;178:R245-R258.2. National Institute for Health and Care Excellence. Psychosis and schizophrenia in children and young people: recognition and management. https://www.nice.org.uk/Guidance/CG155. Published January 2013. Accessed July 17, 2018.Â
The prevalence of type 2 diabetes (T2DM) in persons with severe mental illness (SMI) is up to 3 times higher vs the general population. And while research on the relationship between antipsychotic medications (APs) and cardiometabolic risk is slim, concern is mounting over observed side effects associated with the newer neuroleptic agents – namely weight gain and T2DM.
A new study published in the European Journal of Endocrinology and reviewed in the slides above analyzed the impact of APs on weight gain and intermediate metabolism.
Review of Antipsychotics and Cardiometabolic Risk.1 Rates of T2DM are 2-3 times higher in people with SMI vs the general population and up to 70% of T2DM may be undiagnosed in SMI. Furthermore, health service inequities and APs may worsen CMR in SMI although the overall absolute risk is small and most people on APs will not develop T2DM.
Evidence Base for APs and CMR. Authors searched Medline/PubMed and ClinicalTrials.gov for publications after 2006 using the terms ‘antipsychotic’ and ‘diabetes’ or ‘glucose and found no adequately powered RCTs of glucose or diabetes as primary outcomes in AP trials. However, drug safety reports, observational studies, and meta-analyses did link APs to T2DM and several guidelines on mental illness addressed CMR.
Some APs Have Higher Risk for T2DM vs Others.
- Most weight gain: Olanzapine, clozapine
- Intermediate weight gain: Risperidone, quetiapine
- Least weight gain: Aripipraxole, ziprasidone
- No AP is truly weight neutral
Children/Teens at Increased Risk. The study found that CMR in children and teens may be up to 3 times higher vs the general population and the relative risk of T2DM associated with APs is greatest in those aged 0–24 years.
Effect of APs on T2DM Vary Based on Mental Illness. There was a paucity of evidence between the link of APs and T2DM in children with autism spectrum disorders and tourettes. Also, there was a 2.5 times higher prevalence of T2DM in patients with major depressive disorders vs the general population and limited evidence suggesting APs have less serious metabolic effects in the elderly who suffer from dementia and delirium.
Proposed Mechanism. There was no causal link found between APs and T2DM, however, APs may accelerate the development of T2DM rather than cause it.
Management. Before patients start an AP, physicians will need to check fasting/random blood glucose levels and if A1c is between 6% and 6.5%, intensive lifestyle interventions are needed. During the first year on APs, physicians should check patients fasting/random blood glucose levels at 3 months and A1c at 12 months and once patients are established, check A1c annually if past <6.0. If patients are diagnosed with T2DM while taking APs, physicians should treat as per local T2DM guidelines, T2DM education, and CV risk screening.
Other Management Considerations:
- Reduce health inequalities in SMI with multidisciplinary screening, monitoring, improved prevention, and CMR management.
- Consider a switch to an AP with lower diabetogenic potential.
- Consider GLP-1RA and SGLT2 inhibitors in T2DM.
- Aggressively manage CV risk with annual assessment for diabetes complications.
