Chou Lin-Na, Raji Mukaila A, Holmes Holly M, Kuo Yong-Fang
Department of Physical Therapy and Athletic Training, University of Utah Health, Salt Lake City, Utah, USA
Department of Internal Medicine, Geriatric Division, The University of Texas Medical Branch, Galveston, Texas, USA.
BMJ Open. 2025 Apr 23;15(4):e087694. doi: 10.1136/bmjopen-2024-087694.
To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.
A retrospective cohort study.
A population-based study using the Texas Medicare data.
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).
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.
The main outcome was a new episode of depression, identified by a new depression diagnosis during the follow-up period.
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.
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.
利用2009年至2018年德州医疗保险100%数据库，研究抗糖尿病药物类型与新发抑郁症之间的关联。
一项回顾性队列研究。
一项基于德州医疗保险数据的人群研究。
11种常见的降糖药物类型，单独使用或联合使用：仅二甲双胍、5种不含二甲双胍的治疗方案（仅二肽基肽酶-4抑制剂（DPP4i）、仅磺脲类（SU）、仅噻唑烷二酮类（TZD）、SU/DPP4i和SU/TZD）以及5种含二甲双胍的联合治疗方案（二甲双胍/DPP4i、二甲双胍/SU、二甲双胍/TZD、二甲双胍/SU/DPP4i和二甲双胍/SU/TZD）。
本研究纳入了59057名来自德州医疗保险受益人群队列的2型糖尿病（T2D）患者，这些患者年龄≥66岁，糖尿病药物摄入持续稳定，在2年回顾期内未被诊断为抑郁症或未开具抗抑郁药，且接受医疗保险提供者的常规护理。
主要结局是新发抑郁症，通过随访期间新的抑郁症诊断来确定。
共对59057名T2D患者（平均（标准差）年龄，75.4（6.4）岁；30798名（52.1%）女性）进行了长达96个月的随访。其中，22.5%的患者在5年随访时有新发抑郁症。与仅使用二甲双胍组相比，不含二甲双胍的治疗方案中的患者新发抑郁症风险更高（仅DPP4i组：HR：1.17，95%CI 1.05至1.30；仅SU组：HR：1.06，95%CI 1.01至1.12），但接受含二甲双胍联合治疗的患者之间无显著差异。二甲双胍/TZD和二甲双胍/SU/DPP4i联合治疗方案的新发抑郁症风险低于仅使用二甲双胍组（分别为HR：0.88，95%CI 0.78至0.99和HR：0.83，95%CI 0.71至0.98）。敏感性分析中观察到相同的关联方向。
这项回顾性队列研究发现，接受二甲双胍/TZD和二甲双胍/SU/DPP4i治疗的T2D患者新发抑郁症风险最低。这些发现表明，二甲双胍与其他抗糖尿病药物的某些联合使用可能与新发抑郁症风险降低有关。因此，将抑郁症风险评估纳入常规糖尿病护理并在糖尿病药物类型决策过程中加以考虑可能是有益的，尤其是在停用二甲双胍时。
