Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA

Objectives To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.Design A retrospective cohort study.Setting A population-based study using the Texas Medicare data.Interventions 11 common antihyperglyc...

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Main Authors: Holly M Holmes, Yong-Fang Kuo, Mukaila A Raji, Lin-Na Chou
Format: Article
Language:English
Published: BMJ Publishing Group 2025-04-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/4/e087694.full
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author Holly M Holmes
Yong-Fang Kuo
Mukaila A Raji
Lin-Na Chou
author_facet Holly M Holmes
Yong-Fang Kuo
Mukaila A Raji
Lin-Na Chou
author_sort Holly M Holmes
collection DOAJ
description Objectives To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.Design A retrospective cohort study.Setting A population-based study using the Texas Medicare data.Interventions 11 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).Participants This 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.Results A 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.Conclusions This 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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spelling doaj-art-e7f001b4d199422fb78c63b82d7a7b162025-08-20T02:55:28ZengBMJ Publishing GroupBMJ Open2044-60552025-04-0115410.1136/bmjopen-2024-087694Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USAHolly M Holmes0Yong-Fang Kuo1Mukaila A Raji2Lin-Na Chou35 Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Texas Houston McGovern Medical School, Houston, USASealy Center on Aging, The University of Texas Medical Branch at Galveston, Galveston, Texas, USADivision of Geriatrics and Palliative Medicine, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, Texas, USADepartment of Physical Therapy and Athletic Training, University of Utah Health, Salt Lake City, Utah, USAObjectives To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.Design A retrospective cohort study.Setting A population-based study using the Texas Medicare data.Interventions 11 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).Participants This 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.Results A 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.Conclusions This 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.https://bmjopen.bmj.com/content/15/4/e087694.full
spellingShingle Holly M Holmes
Yong-Fang Kuo
Mukaila A Raji
Lin-Na Chou
Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
BMJ Open
title Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
title_full Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
title_fullStr Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
title_full_unstemmed Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
title_short Impact of antidiabetic medication type on a new episode of depression: a retrospective cohort study in Texas, USA
title_sort impact of antidiabetic medication type on a new episode of depression a retrospective cohort study in texas usa
url https://bmjopen.bmj.com/content/15/4/e087694.full
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