Efficacy and Safety of Antidiabetic Agents for Major Depressive Disorder and Bipolar Depression: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Background: This meta-analysis aimed to determine the efficacy and safety of antidiabetic agents in the treatment of major depressive disorder and bipolar depression. Methods: Randomized controlled trials (RCTs) of antidiabetic agents in major depressive disorder or bipolar depression were searched in three electronic databases and three clinical trial registry websites from their inception up to October 2023. The differences in changes in the depression rating scale scores from baseline to endpoint or pre-defined sessions, response rate, remission rate, rate of side effects and dropout rate between antidiabetic agents and placebo were meta-analyzed. Results: Six RCTs involving 399 participants were included in the final meta-analysis, which did not find that antidiabetics outperformed the placebo in reducing depressive symptoms. The standardized mean difference (SMD) in the depression scores from baseline to endpoint was 0.25 (95% CI -0.1, 0.61). However, a subgroup analysis found a significant difference between antidiabetics and placebos in reducing depressive symptoms in Middle Eastern populations, with an SMD of 0.89 (95% CI 0.44, 1.34). Conclusions: The current meta-analysis does not support the efficacy of antidiabetics being superior to the placebo in the treatment of unipolar and bipolar depression. However, a subgroup analysis indicates that patients from the Middle East may benefit from adding an antidiabetic medication to their ongoing medication(s) for their depression. Larger studies with good-quality study designs are warranted.