| 摘要: | 第二型糖尿病是一種慢性代謝疾病，約有40%糖尿病患者合併有糖尿病腎病變，進而演變成慢性腎臟病，因此糖尿病與慢性腎臟病共同照護的重要性不容小覷。糖尿病患者時常合併其他慢性疾病導致用藥種類繁多，因此藥物治療方面應選擇同時具有良好的血糖控制並對腎臟有保護作用的降血糖藥物，而探討現有之降血糖藥物是否能有心腎保護作用達到一藥多用的效果，不僅能提高患者生活品質，就預防醫學的角度也是相當有效益的，本研究旨在探究本身有卓越降血糖功效的Glucagon-like peptide-1 receptor agonist (GLP-1 RA)類藥物是否同時具有腎臟保護作用，並深入探討GLP-1 RA中各個成分用於糖尿病患者對其腎功能的影響。
本研究為回溯觀察性研究，資料來源為臺北醫學大學臨床研究資料庫(TMUCRD)及TriNetX兩個資料庫，探討GLP-1 RA(Dulaglutide、Liraglutide及Semaglutide)於第二型糖尿病併慢性腎病患者之腎臟保護效果，對照組為Linagliptin。研究分為兩個部分，TMUCRD方面收錄2012年12月至2022年12月於北萬雙三院就診之患者中符合以下條件者：1) 患有第二型糖尿病、2) ?18歲、3) 曾使用GLP-1 RA(Dulaglutide、Liraglutide、Semaglutide)或Linagliptin、4) 初始腎絲球過濾率eGFR介於15-59 ml/min/1.73 m^2，研究終點事件為索引日期至少90天後發生之持續性(連續3次檢驗)eGFR較研究起始時降低?50%、持續性(連續3次檢驗) eGFR<15 ml/min/1.73 m^2、任一次洗腎紀錄或腎因性死亡，經傾向分數1：4配對後以次分布競爭風險模型估算出腎臟複合式結局於GLP-1 RA與對照組的次分布風險比(SHR, Subdistribution hazard ratio)，並再擷取eGFR 30-59 ml/min/1.73 m^2之患者進行亞組分析。TriNetX方面收錄條件同TMUCRD，研究終點事件定義為索引日期至少90天後任一次事件之eGFR<15 ml/min/1.73 m^2、任一次洗腎事件或需腎臟移植，經傾向分數1：1配對後以Kaplan-Meier survival analysis估算出以下eGFR介於15-59 ml/min/1.73 m^2族群的風險比(HR, Hazard ratio)：1) GLP-1 RA與對照組、2) Dulaglutide與對照組、3) Liraglutide與對照組、4) Semaglutide與對照組。
研究結果顯示eGFR 15-59 ml/min/1.73 m^2之患者，TMUCRD中GLP-1 RA與對照組於腎臟複合式結局之SHR為0.56(95% CI, 0.34-0.94)，TriNetX中GLP-1 RA與對照組之HR為0.255(95% CI, 0.228-0.285)、Dulaglutide與對照組之HR為0.300(95% CI, 0.258-0.349)、Liraglutide與對照組之HR為0.230(95% CI, 0.174-0.304)、Semaglutide與對照組之HR為0.212(95% CI, 0.172 -0.261)。eGFR 30-59 ml/min/1.73 m^2之患者，TMUCRD中GLP-1 RA與對照組於腎臟複合式結局之SHR為0.32(95% CI, 0.16-0.63)。
基於GLP-1 RA於第二型糖尿病併慢性腎病患者之腎臟保護效果的正向研究結果，針對肥胖、無法耐受SGLT2i副作用、腎功能有輕微受損趨勢、動脈粥樣硬化心血管疾病高風險、吞嚥困難、希望減少給藥次數、且不排斥打針的患者，應及早推薦選擇GLP-1 RA來同時達到預防腎功能惡化、減重、預防心血管疾病等除了降血糖以外的多重功效。
Type 2 diabetes is a chronic metabolic disease, with approximately 40% of patients developing diabetic nephropathy, which can lead to chronic kidney disease. Therefore, the importance of joint care for diabetes and chronic kidney disease cannot be underestimated. Diabetic patients often have other chronic diseases, leading to the use of a variety of medications. Hence, it is crucial to choose antidiabetic drugs that not only control blood sugar effectively but also offer renal protection. Investigating whether existing antidiabetic drugs can provide cardiorenal protection to achieve multifunctional effects can significantly enhance patient quality of life. This study aims to explore whether drugs in the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class, known for their excellent hypoglycemic effects, also offer renal protection and to examine the impact of various components of GLP-1 RA on renal function in diabetic patients.
This retrospective observational study uses data from Taipei Medical University Clinical Research Database (TMUCRD) and TriNetX to examine the renal protective effects of GLP-1 RAs (Dulaglutide, Liraglutide, and Semaglutide) in patients with type 2 diabetes and chronic kidney disease, with Linagliptin as the control group. The study is divided into two parts: TMUCRD included patients from December 2012 to December 2022 meeting the following criteria: 1) Diagnosed with type 2 diabetes, 2) Aged ?18, 3) Previously treated with GLP-1 RAs (Dulaglutide, Liraglutide, Semaglutide) or Linagliptin, 4) Initial eGFR ranging from 15-59 ml/min/1.73 m?. The endpoint events were defined as a persistent decrease in eGFR ?50% from baseline, persistent eGFR <15 ml/min/1.73 m?, any dialysis record, or renal-related death occurring at least 90 days after the index date. After 1:4 propensity score matching, subdistribution hazard ratio (SHR) for composite renal outcome between GLP-1 RA and control group was estimated using a competing risk model. Subgroup analysis was conducted for patients with eGFR 30-59 ml/min/1.73 m?. TriNetX included patients with same criteria as TMUCRD, with endpoint events defined as eGFR <15 ml/min/1.73 m?, any dialysis record, or kidney transplantation at least 90 days after the index date. Hazard ratio (HR) was estimated using Kaplan-Meier survival analysis after 1:1 propensity score matching.
For patients with eGFR 15-59 ml/min/1.73 m?, SHR in TMUCRD for composite renal outcome was 0.56 (95% CI, 0.34-0.94), and HR in TriNetX for GLP-1 RA vs. control group was 0.255 (95% CI, 0.228-0.285), Dulaglutide vs. control group was 0.300 (95% CI, 0.258-0.349), Liraglutide vs. control group was 0.230 (95% CI, 0.174-0.304), and Semaglutide vs. control group was 0.212 (95% CI, 0.172-0.261). For patients with eGFR 30-59 ml/min/1.73 m?, SHR in TMUCRD for composite renal outcome was 0.32 (95% CI, 0.16-0.63).
Based on the positive outcomes of GLP-1 RAs in renal protection for patients with type 2 diabetes and chronic kidney disease, it is recommended to consider early use of GLP-1 RAs for patients at high risk of arteriosclerotic cardiovascular disease, those who cannot tolerate SGLT2i side effects, or those with mild renal impairment to achieve multiple benefits beyond glycemic control, such as preventing renal function deterioration, weight loss, and preventing cardiovascular diseases. |
