Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Abstract

Summary Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP‐1RAs suggest that these medications are associated with a high prevalence of mild–moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP‐1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic‐induced weight gain is worth considering in Australia. This would bring us into line with other countries.

Comparison of the Safety and Weight Loss Efficacy of Metformin and Liraglutide in Psychiatric Outpatients at a University Hospital: A Retrospective Chart Review

“…Although management of patients' mental health is important [32], the use of MET for this purpose remains limited [33]; this lack of widespread use may partially explain the relatively low dosage of MET in the present study. MET carries a minimal risk of severe side effects, such as hypoglycemia; the most serious side effect, lactic acidosis, typically occurs only in patients with severe renal impairment or when MET is used at very high dosages [34].…”

The Being Equally Well national policy roadmap: providing better physical health care and supporting longer lives for people living with serious mental illness

“…14 In addition, a review that considered the cardiometabolic effects of using antidiabetic medications in people with serious mental illness supports a recommendation that these drugs be made available through the Pharmaceutical Benefits Scheme. 15 …”

Practice and system improvements for better physical health and longer lives for people living with serious mental illness

“…Although some countries use antidiabetic medication as a preventive therapy, this is not approved in Australia. The case for early use of antidiabetic medication is discussed in the supplement 8 . Lessons from the use of clozapine are revealing.…”