Comparing the Effects of Antidiabetic Medications on Depression: Network meta-analysis

Nearly 4 million people in the UK have type 2 diabetes (T2DM), and 20-33% of them have moderate to severe depression symptoms. Without early intervention, these individuals are 2-3 times more likely to develop clinical depression, which further complicates T2DM management. Antidiabetic medications are primarily prescribed for glycaemic control. Recent meta-analyses suggest some antidiabetic medications (e.g. metformin, pioglitazone, and semaglutide) may also alleviate depressive symptoms. This potential benefit may be due to their anti-inflammatory, antioxidative, and neuroendocrine effects and weight loss. However, most interventions have not been directly compared them in head-to-head trials, leaving it unclear which of the 30+ available medications provide better benefits. Given 66 million prescriptions are issued annually for diabetes in England, addressing this research gap is crucial. Identifying medications that manage both blood sugar and depression could help reduce the healthcare burden and NHS costs associated with both conditions. We will 1) review randomised clinical trials in people with T2DM and use network meta-analysis to compare the effects of antidiabetic medications on changes in depression severity, measured by mean change from baseline to post-treatment on standardised validated scales; and 2) collaborate with patients to understand their experiences and expectations on managing T2DM and depressive symptoms.