摘要

第二型糖尿病 (type 2 diabetes mellitus, T2DM) 是一個心臟、腎臟和代謝相關聯的疾病，通常合併多種併發症包含動脈粥狀硬化心血管疾病 (atherosclerotic cardiovascular disease, ASCVD)、心衰竭 (heart failure, HF) 和慢性腎疾病 (chronic kidney disease, CKD)。Sodium-glucose co-transporter 2 inhibitor (SGLT2i) 具有多樣化作用包含腎臟的機轉（增加糖尿、利鈉尿、紅血球生成素製造、腎小管腎絲球回饋，減少腎絲球內壓力和過濾率、蛋白尿、腎小管工作負荷）；心血管和代謝的機轉（加強胰島素敏感性、酮生成、心肌能量活力和心臟收縮，減少心臟前後負荷、血壓、心肌氧化壓力、發炎和纖維化）。在臨床試驗中顯示，SGLT2i 可明顯減少主要試驗結果，包含三項主要不良心血管事件、CV 死亡、HF 住院、CKD 惡化、因腎臟或CV原因死亡等風險。已開發國家和國際組織正快速更新SGLT2i 的治療建議與指引，包含了DM和非DM病人。然而在早期的臨床試驗觀察到SGLT2i 引起幾項副作用事件，包括低血糖、低血壓、泌尿道感染、生殖器感染、糖尿病酮酸中毒、下肢截肢、骨折等，儘管其中一些事件很少見，但可能導致嚴重和潛在危及生命的併發症，突顯了嚴密監測病患的重要性。此篇文獻回顧文章討論SGLT2i 於合併有或無DM 病人，減少CV 及腎臟疾病風險之生理學機轉與臨床試驗療效，也探討目前臨床指引之建議、藥物安全性考量和藥師在病人照護的角色。

 

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition commonly associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). Sodiumglucose co-transporter 2 inhibitor (SGLT2i) exert pleiotropic effects, including renal mechanisms (increase glycosuria, natriuresis, erythropoietin production, and tubuloglomerular feedback, while reducing intraglomerular pressure , filtration rate, proteinuria, and tubular workload) and cardiovascular and metabolic mechanisms (enhancing insulin sensitivity, ketone production, myocardial energetics, and cardiac contractility, while lowering cardiac preload and afterload, blood pressure, myocardial oxidative stress, inflammation and fibrosis). Clinical trials have shown that SGLT2i significantly reduce three-point major adverse cardiovascular events (MACE), cardiovascular (CV) death, hospitalization for HF, CKD progression, and death from renal or CV causes. Developed countries and international organizations are rapidly updating treatment recommendations and guidelines for the use of SGLT2i in patients with or without diabetes. However, several adverse events have been observed in early clinical trials, including hypoglycemia, hypotension, urinary tract infections, genital infections, diabetic ketoacidosis, lower limb amputation, and bone fractures. Although some of these events are rare, they may lead to serious and potentially life-threatening complications, underscoring the importance of close patient monitoring. This article reviews the physiologic mechanisms and clinical trial evidence supporting the use of SGLT2i to reduce cardiovascular and renal risks in patients with or without diabetes. It also discusses current clinical guideline recommendations, drug safety considerations, and the role of pharmacists in patient care.

 

 

Submitted for publication: 2024.11.13; Accepted for publication: 2025.3.20