Co-prescription of metformin and antipsychotics in severe mental illness: a UK primary care cohort study

Abstract

Background Metformin is a pharmacological candidate to mitigate second-generation antipsychotic (SGA)-induced weight gain in patients diagnosed with severe mental illnesses (SMI). Objective To determine the incidence, prevalence and demographic patterns of metformin co-prescription among patients diagnosed with SMI initiating SGAs. To estimate the impact of metformin co-prescription on weight over 2 years post-SGA initiation. Methods A cohort study of patients diagnosed with SMI initiating aripiprazole, olanzapine, quetiapine or risperidone in 2005-2019 using primary care data from Clinical Practice Research Datalink. We estimated cumulative incidence and period prevalences of co-prescription and explored prescribing differences by demographic and clinical factors. We compared weight change among patients prescribed an SGA-only versus an SGA plus metformin, accounting for confounders using linear regression. Findings Among 26 537 patients initiating SGAs, 4652 were ever prescribed metformin and 21 885 were not. The two-year incidence of first metformin prescription was 3.3%. The SGA plus metformin group were more ethnically diverse, had greater social deprivation, more comorbidities and higher baseline weight (mean 90.4 vs 76.8 kg). By 2 years post-SGA initiation, mean weight in the SGA-only group had changed by +4.16% (95% CI -1.26 to +9.58) compared with -0.65% (95% CI -4.26 to +2.96) in the SGA plus metformin group. After confounder adjustment, the 2-year mean difference in weight with metformin co-prescription was -1.48 kg (95% CI -4.03 to 1.07) among females and -1.84 kg (95% CI -4.67 to 0.98) among males. Conclusion Metformin is infrequently co-prescribed, despite apparent efficacy and guidelines. Clinical implications Primary and secondary care collaboration should be strengthened and barriers to co-prescribing addressed.