ArticleBMJ open2025
Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA.
Article in BMJ open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.
designA retrospective cohort study.
settingA population-based study using the Texas Medicare data.
interventions11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).
participantsThis study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, had consistent diabetes medication intake, were not diagnosed with depression or prescribed antidepressants during the 2-year look-back period and received regular care from Medicare providers. MAIN OUTCOMES AND MEASURES: The main outcome was a new episode of depression, identified by a new depression diagnosis during the follow-up period.
resultsA total of 59 057 T2D patients (mean (SD) age, 75.4 (6.4) years; 30 798 (52.1%) female) were followed up to 96 months. Of these, 22.5% patients had a new episode of depression at the 5-year follow-up. Compared with the metformin-only group, patients in the non-metformin-containing regimens had a higher risk of new episode depression (HR: 1.17, 95% CI 1.05 to 1.30 for DPP4i-only; HR: 1.06, 95% CI 1.01 to 1.12 for SU-only), but there was no significant difference among patients receiving metformin-containing combination therapy. Metformin/TZD and metformin/SU/DPP4i combination treatments had a lower risk of new episodes of depression than metformin-only (HR: 0.88, 95% CI 0.78 to 0.99 and HR: 0.83, 95% CI 0.71 to 0.98 separately). The same direction of association was observed in sensitivity analyses.
conclusionsThis retrospective cohort study found that T2D patients treated with metformin/TZD and metformin/SU/DPP4i had the lowest risk of new episodes of depression. These findings suggest that certain combinations of metformin with other antidiabetic medications may be associated with a reduced risk of new-onset depression. Therefore, it could be beneficial to incorporate depression risk evaluation into routine diabetes care and consider it in the decision-making process for diabetes medication types, especially when deprescribing metformin.
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