Department of Pharmacy Practice and Administration, School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, West Hartford, CT, USA.
Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, CT, USA.
Ann Pharmacother. 2024 Sep;58(9):935-946. doi: 10.1177/10600280231211179. Epub 2023 Nov 28.
To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management.
A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of "sotagliflozin," "Inpefa," or "LX4211."
All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information.
Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88).
While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors.
Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors.
描述钠-葡萄糖共转运蛋白（SGLT）1 和 SGLT2 的双重抑制剂索格列净在心力衰竭（HF）管理中的药理学、临床疗效和安全性证据。
使用 PubMed、MEDLINE 和 clinicaltrials.gov 对 2012 年 1 月至 2023 年 9 月期间发表的研究进行了文献检索，检索词为“索格列净”、“Inpefa”或“LX4211”。
考虑了所有可用的英文研究。如果研究调查了药物的药理学、疗效或安全性信息，则将其纳入研究。
两项索格列净的 3 期临床试验，即 SOLOIST-WHF 和 SCORED，评估了索格列净与安慰剂在 2 型糖尿病（T2DM）患者中的疗效。SOLOIST-WHF 报告称，索格列净组的心血管和 HF 事件发生率呈统计学降低（风险比[HR] = 0.67，95%CI = 0.52-0.85），而 SCORED 发现，在 T2DM、慢性肾脏病（CKD）和心血管疾病风险因素的患者中，索格列净组的心血管事件发生率呈统计学显著降低（HR = 0.74，95%CI = 0.63-0.88）。
与现有药物相比，对患者护理和临床实践的相关性：虽然索格列净的批准扩大了 HF 患者的治疗选择，但 SGLT2 抑制剂达格列净和恩格列净在 HF 中的使用数据更多，在 CKD 患者中具有额外的风险降低益处，并且批准用于 T2DM。尽管索格列净的更广泛的批准适应症是存在 T2DM，但索格列净的标志性试验需要有 T2DM 的先前诊断。由于已经确立的 SGLT2 抑制剂的证据和益处，以及与 SGLT2 抑制剂比较的需要，因此尚不清楚索格列净将在 HF 的治疗中采用。
鉴于目前可用证据的局限性，包括由于主要终点的改变、未裁决事件以及未达到原始功率计算而难以完全解释试验结果，需要进一步研究以确定与 SGLT2 抑制剂相比，索格列净的获益。
