(SLA-014) Metformin Use and Risk of Depression in Patients with Diabetes

Background: The association between metformin use and depression remained controversial. Observational studies may subject to possible confounding by indication when analyzing this issue.

Objectives: To evaluate the association between metformin use and risk of depression in patients with diabetes using the clone censor weight (CCW) approach and trend in trend (TIT) analysis.

Methods: We emulated a target trial using data from the National Health Insurance Research Database (NHIRD). We included patients with diabetes between 2002 and 2018 and excluded those with any psychiatric disorders in the past years to avoid misclassification of outcome. We employed the CCW approach and assigned patients to exposure group based on a 6-month grace period following diabetes diagnosis. Inverse probability weighting was applied to address artificial censoring. We performed weighted pooled logistic regression and non-parametric bootstraps to estimate the risk of depression and calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Additionally, we applied a TIT analysis, which was considered as an unbiased analysis, and compared the result estimates from CCW and TIT.

Results: A total of 127,886 patients with diabetes were included. The mean age was 62.2 (standard deviation 16.3) years, and 49.1% were male. In CCW, we observed metformin use was not associated with the risk of depression (OR 0.97 95% CI: 0.92–1.04). However, the TIT analysis indicated an association of reduced risk of depression but without statistical significance (OR 0.80 95% CI: 0.40–1.20).

Conclusions: We found no association from CCW between metformin use and risk of depression, but the results were different when the issue of potential confounding by indication was addressed in TIT analysis. The TIT may subject to potential type 2 error that requires future study with larger sample size to provide more stable assessment.