The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacoepidemiology and Drug Safety Pub Date : 2024-08-01 DOI:10.1002/pds.5876

Tiansheng Wang, Dongze Ji, Til Stürmer, Sherin Ismail, Shujie Dong, Peng Shen, Hongbo Lin, Luwen Shi, Xiaodong Guan, Yang Xu

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Abstract

Purpose: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability.

Methods: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis.

Results: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses.

Conclusions: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

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葡萄糖钠转运体 2 抑制剂对血红蛋白 A1c 变异性和急性肾损伤的影响：因果中介分析

目的：较低的血红蛋白 A1c（HbA1c）变异性在钠葡萄糖共转运体-2 抑制剂（SGLT2i）对急性肾损伤（AKI）影响中的作用仍不清楚。我们比较了 SGLT2i 和二肽基肽酶 4 抑制剂 (DPP4i) 启动者之间的 AKI 风险。此外，我们还旨在探索 SGLT2i 对 AKI 风险的影响在多大程度上是通过降低长期 HbA1c 变异性来介导的：利用鄞州地区医疗数据库2018-2022年的数据，我们纳入了新使用SGLT2i或DPP4i的成年2型糖尿病患者。采用逆概率治疗加权Cox比例危险模型、中位回归模型和因果中介分析，比较了SGLT2i与DPP4i对AKI、HbA1c变异性和AKI通过HbA1c变异性的影响：中位随访时间为1.76年，共纳入19 717名2型糖尿病成人患者（SGLT2i，n = 6008；DPP4i，n = 13 709）。调整后，SGLT2i 与 DPP4i 的 AKI 危险比为 0.79（95% 置信区间 [CI] 0.64-0.98）。调整后的中位 HbA1c 变异性评分（HVS）和 HbA1c 降低率的差异分别为-16.67%（95% CI：-27.71% 至-5.62%）和-1.98%（95% CI：-14.34% 至 10.38%）。此外，与 SGLT2i 相关的较低 AKI 风险通过 HVS 中度介导（22.77%）。这些结果在不同的亚组和敏感性分析中保持一致：与 DPP4i 相比，SGLT2i 可通过 HbA1c 变异性中度介导较低的 AKI 风险。这些发现加深了我们对 SGLT2i 对 AKI 影响的理解，并强调了在糖尿病治疗和管理中考虑 HbA1c 变异性的重要性。

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来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.