Medical Director, Centre for Diabetes and Endocrine Care, Srinagar, Jammu Kashmir.
Pharmaceutical Geriatric Medicine, DGM Medical Affairs, Medical Affairs Team, Alkem Labs., Mumbai, Maharashtra.
J Assoc Physicians India. 2021 Sep;69(9):11-12.
Dapagliflozin is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors which was approved by USFDA in management of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise to improve glycemic control in adults initially, followed by to reduce the risk of hospitalization for heart failure (HHF) in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors. Most recently, it is approved to reduce the risk of cardiovascular death and in adults with heart failure (HF) with reduced ejection fraction (NYHA class II-IV). Dapagliflozin has been studied in a wide range of patients with diabetes and plethora of evidence has confirmed its efficacy as a monotherapy as well as an add-on to the oral therapies and insulin, when compared to placebo. Additional advantages include weight reduction which has been consistently demonstrated in Phase III studies and good tolerability. Also there is a demonstrable reduction in systolic blood pressure in patients treated with SGLT2 inhibitors. DECLARE TIMI 58 study clearly demonstrated that Dapagliflozin was non inferior in reducing major adverse cardiovascular events (MACE) in patients with T2DM and high CV risk compared with placebo. 27% risk reduction in heart failure hospitalisation was noted along without increased risk of amputation. DAPA HF evaluated the efficacy and safety of the dapagliflozin in patients with HF and reduced ejection fraction, irrespective of the presence or absence of diabetes. Patients with symptomatic HF due to reduced ejection fraction treated with dapagliflozin had positive outcomes with reduction in cardiovascular deaths and HF events. The DAPA-CKD trial which was conducted to assess the efficacy and safety of dapagliflozin in patients with chronic kidney disease (CKD), with or without type 2 diabetes found that it significantly lowered the risk of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes in patients with CKD, regardless of the presence or absence of diabetes. Ongoing trials like DELIVER, DAPA ACT HF-TIMI 68, DICTATE-AHF, HF readmission study, DAPA MI Study, Effectiveness of Dapagliflozin for Weight Loss, will throw more light on the precise effects of dapagliflozin in several clinical scenarios. To conclude - Dapagliflozin was well studied not only in T2DM but also in HF and CKD patients with positive results and good safety profile.
达格列净是首个被美国食品药品监督管理局（FDA）批准用于治疗 2 型糖尿病（T2DM）的新型降糖药物，属于钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，与饮食和运动联合使用，改善成年人的血糖控制，最初用于治疗 2 型糖尿病，随后降低成年 T2DM 伴心血管疾病或多种心血管危险因素患者心力衰竭（HF）住院风险。最近，它被批准用于降低伴有射血分数降低（NYHA II-IV 级）的心力衰竭（HF）成人的心血管死亡风险。达格列净已在广泛的糖尿病患者中进行了研究，大量证据证实了其作为单药治疗以及与口服药物和胰岛素联合治疗的疗效，与安慰剂相比。其额外的优势包括在 III 期研究中一致证明的体重减轻和良好的耐受性。此外，接受 SGLT2 抑制剂治疗的患者的收缩压也有明显降低。DECLARE TIMI 58 研究清楚地表明，与安慰剂相比，达格列净在降低 T2DM 伴高心血管风险患者的主要不良心血管事件（MACE）方面不劣效。研究还观察到心力衰竭住院率降低 27%，同时没有增加截肢风险。DAPA-HF 评估了达格列净在射血分数降低的心力衰竭患者中的疗效和安全性，无论是否存在糖尿病。接受达格列净治疗的射血分数降低的有症状心力衰竭患者的心血管死亡和心力衰竭事件发生了积极的结果。DAPA-CKD 试验旨在评估达格列净在伴有或不伴有 2 型糖尿病的慢性肾脏病（CKD）患者中的疗效和安全性，结果发现，无论是否存在糖尿病，它都能显著降低 CKD 患者估算肾小球滤过率持续下降至少 50%、终末期肾病或因肾脏或心血管原因死亡的风险。正在进行的临床试验，如 DELIVER、DAPA-ACT HF-TIMI 68、DICTATE-AHF、HF 再入院研究、DAPA-MI 研究、达格列净对体重减轻的有效性，将进一步阐明达格列净在几种临床情况下的确切作用。总之，达格列净不仅在 2 型糖尿病中进行了广泛研究，在心力衰竭和伴有射血分数降低的慢性肾脏病患者中也进行了积极的研究，具有良好的安全性。
