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

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.