Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
BMJ Open Diabetes Res Care. 2022 Jun;10(3). doi: 10.1136/bmjdrc-2021-002636.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now recommended in guidelines for persons with type 2 diabetes mellitus (T2DM) and at risk of advanced kidney disease as part of the glucose-lowering regimen.
To explore the optimal threshold at which to initiate SGLT2 inhibitor therapy, we conducted an observational study analyzed under a counterfactual framework. This study used the electronic healthcare database in Japan, comprising data from approximately 20 million patients at approximately 160 medical institutions. Persons with T2DM with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m in April 2014 were eligible. The primary end point was the composite of renal deterioration (>40% decline in eGFR) and the development of eGFR<30 mL/min/1.73 m. We estimated the risk of the composite end point occurring over 77 months in different scenarios, such as early or delayed intervention with SGLT2 inhibitors for uncontrolled diabetes at different hemoglobin A1c (HbA) thresholds. The parametric g-formula was used to estimate the risk of the composite end point, adjusting for time-fixed and time-varying confounders.
We analyzed data from 36 237 persons (149 346 person-years observation), of whom 4679 started SGLT2 inhibitor therapy (9470 person-years observation). Overall, initiating SGLT2 inhibitor therapy was associated with a 77-month risk reduction in the end point by 1.3-3.7%. The largest risk reduction was observed within 3 months of initiation once the HbA level exceeded 6.5% (risk reduction of 3.7% (95% CI 1.6% to 6.7%)) compared with a threshold of 7.0% or higher.
Our analyses favored early intervention with SGLT2 inhibitors to reduce the renal end point, even for persons with moderately controlled HbA levels. Our findings also suggest caution against clinical inertia in the care of diabetes.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂现被推荐用于治疗 2 型糖尿病（T2DM）患者和有进展为晚期肾病风险的患者，作为降低血糖方案的一部分。
为了探索启动 SGLT2 抑制剂治疗的最佳阈值，我们进行了一项观察性研究，该研究采用反事实框架进行分析。本研究使用了日本的电子医疗数据库，该数据库包含来自大约 160 家医疗机构的约 2000 万名患者的数据。2014 年 4 月时估算肾小球滤过率（eGFR）≥30 mL/min/1.73 m 的 T2DM 患者符合条件。主要终点是肾功能恶化（eGFR 下降>40%）和 eGFR<30 mL/min/1.73 m 的复合终点。我们在不同的情况下估计了 77 个月内复合终点发生的风险，例如在不同的血红蛋白 A1c（HbA）阈值下，对未控制的糖尿病进行早期或延迟干预使用 SGLT2 抑制剂。使用参数 g 公式估计复合终点的风险，同时调整时间固定和时间变化的混杂因素。
我们分析了 36237 名患者（149346 人年观察）的数据，其中 4679 名患者开始使用 SGLT2 抑制剂治疗（9470 人年观察）。总体而言，与 HbA 水平≥7.0%相比，一旦 HbA 水平超过 6.5%，启动 SGLT2 抑制剂治疗可在 77 个月内降低终点风险 1.3-3.7%。在启动治疗后 3 个月内，风险降低幅度最大（3.7%，95%CI 1.6%至 6.7%）。
我们的分析倾向于早期使用 SGLT2 抑制剂来降低肾脏终点，即使对于 HbA 水平得到较好控制的患者也是如此。我们的研究结果还表明，在糖尿病治疗中应谨慎避免临床惰性。
