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

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.