The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Eur Heart J Qual Care Clin Outcomes. 2023 Jun 21;9(4):397-407. doi: 10.1093/ehjqcco/qcac040.
The frequency of an acute increase in serum creatinine (sCr) of >30%, following treatment of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and its clinical implications in patients with type 2 diabetes remains unclear.
We used medical data from a multicentre health care provider in Taiwan and recruited 11 657 and 8117 diabetic patients with baseline/follow-up sCr data available within 12 weeks of SGLT2i and dipeptidyl peptidase-4 inhibitor (DPP4i) treatment from 1 June 2016 to 31 December 2018. Participants receiving SGLT2i or DPP4i were categorized by initial sCr change into three groups: >30% sCr increase, 0-30% increase, or no-sCr increase. Participants receiving SGLT2i were associated with a higher proportion of sCr increase of 0-30% (52.7 vs. 42.6%) but a lower proportion of sCr increase of >30% (5.9 vs. 9.6%) when compared with DPP4i. In contrast to DPP4i, the mean estimated glomerular filtration rate over time became stable after 24 weeks in three categories of sCr increase following SGLT2i initiation. Compared with no sCr increase, an initial sCr increase of >30% was associated with a higher risk of major adverse cardiovascular events {adjusted hazard ratio (aHR): 2.91, [95% confidence interval (95% CI):1.37-6.17]}, heart failure hospitalization (HHF) [aHR:1.91, (95% CI:1.08-3.40)], and composite renal outcome [aHR:1.53, (95% CI:1.05-2.25)] in the SGLT2i group; an initial sCr increase of >30% associated with a higher risk of HHF and composite renal outcome in the DPP4i group after multivariate adjustment. Overall, participants receiving SGLT2i were associated with a lower risk of HHF [aHR:0.64, (95% CI:0.48-0.85)] and composite renal outcomes [aHR:0.40, (95% CI:0.34-0.48)] compared with DPP4i after multivariate adjustment, and the treatment benefit was persistent across three categories of sCr increase (P interaction > 0.05).
A modest increase in serum creatinine (<30%) was common following SGLT2i initiation, and was not associated with worse clinical outcomes, therefore should not stop therapy prematurely, but a larger increase in creatinine following drug therapy was not typical and should raise concern and review of the patient.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）治疗后血清肌酐（sCr）升高>30%的频率及其在 2 型糖尿病患者中的临床意义尚不清楚。
我们使用了来自台湾一家多中心医疗机构的医疗数据，招募了 11657 名和 8117 名糖尿病患者，他们在 2016 年 6 月 1 日至 2018 年 12 月 31 日期间接受 SGLT2i 和二肽基肽酶-4 抑制剂（DPP4i）治疗后 12 周内有基线/随访 sCr 数据。根据初始 sCr 变化，将接受 SGLT2i 或 DPP4i 治疗的患者分为三组：sCr 升高>30%、0-30%升高或 sCr 无升高。与 DPP4i 相比，SGLT2i 组 sCr 升高 0-30%的比例较高（52.7% vs. 42.6%），sCr 升高>30%的比例较低（5.9% vs. 9.6%）。与 DPP4i 相比，在 SGLT2i 治疗开始后 24 周内，三种 sCr 升高类别中，肾小球滤过率的估计值在时间上趋于稳定。与 sCr 无升高相比，初始 sCr 升高>30%与主要不良心血管事件（校正后的危险比[aHR]：2.91，95%置信区间[95%CI]：1.37-6.17）、心力衰竭住院（HHF）[aHR：1.91，95%CI：1.08-3.40]和复合肾脏结局[aHR：1.53，95%CI：1.05-2.25]的风险增加相关；在多变量调整后，SGLT2i 组中 sCr 升高>30%与 HHF 和复合肾脏结局的风险增加相关，而 DPP4i 组中 sCr 升高>30%与 HHF 和复合肾脏结局的风险增加相关。总体而言，与 DPP4i 相比，SGLT2i 组的 HHF [aHR：0.64，95%CI：0.48-0.85]和复合肾脏结局[aHR：0.40，95%CI：0.34-0.48]的风险降低，多变量调整后治疗效果持续存在于三种 sCr 升高类别中（P 交互>0.05）。
SGLT2i 治疗后血清肌酐（sCr）适度升高（<30%）较为常见，与不良临床结局无关，因此不应过早停药，但药物治疗后肌酐升高较大则不典型，应引起关注并重新评估患者。
