Sotagliflozin is a dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibitor that reduces heart failure (HF) outcomes in adults with type 2 diabetes and high cardiovascular (CV) risk.^{1, 2} Understanding the time-to-benefit with therapy can inform the urgency with which to prescribe.

SCORED was a randomized, double-blind study of patients with type 2 diabetes (glycated haemoglobin ≥7%), chronic kidney disease (estimated glomerular filtration rate 25–60 ml/min/1.73 m² of body surface area), and additional risk factors for CV disease.¹ Patients were randomized 1:1 to sotagliflozin or placebo. The primary endpoint was a composite of CV death, hospitalization for HF, or urgent visit for HF. The secondary endpoint was total hospitalizations for HF and urgent visits for HF.

In this post hoc analysis, the hazard ratio (HR) of sotagliflozin compared with placebo was assessed for each outcome continuously from time of randomization. The exact day after randomization when the treatment effect of therapy reached statistical significance (p < 0.05) and remained statistically significant for the duration of follow-up was determined.

SCORED was approved by the relevant health authorities, institutional review boards, or ethics committees at each trial site.

The final cohort consisted of 10 584 patients. Median age of this group was 69 years, with 44.9% female. Median follow-up was 16.0 months. Over the entire study period, sotagliflozin compared with placebo reduced the risk of the primary endpoint (HR 0.74; 95% confidence interval [CI] 0.63–0.88; p < 0.001), with 5.6 events per 100 person-years in the sotagliflozin group and 7.5 events per 100 person-years in the placebo group. A sustained significant reduction in the outcome was observed at 95 days after randomization (HR 0.70, 95% CI 0.50–0.98; Figure 1A).

Sotagliflozin compared with placebo similarly reduced the risk of the secondary endpoint (HR 0.67, 95% CI 0.55–0.82; p < 0.001), with 3.5 events per 100 person-years in the sotagliflozin group and 5.1 events per 100 person-years in the placebo group. A sustained significant reduction was observed at 115 days after randomization (HR 0.70, 95% CI 0.49–1.00; Figure 1B).

Among patients in SCORED, sotagliflozin improved HF outcomes, with statistically significant improvements observed as soon as 95 days from randomization. This reduction was sustained throughout the study period. The rapid time to clinical benefit with sotagliflozin in these clinically stable outpatients indicates the importance of immediate initiation of therapy. Beneficial effects were observed early, with the continuous analysis suggesting a steady state of treatment benefit in the first month, which may indicate rapid biological benefits (Figure 1). Clinical inertia in prescribing SGLT inhibitor therapy can result in missed opportunities for preventing HF events,³ and starting therapy quickly, potentially at index admission, could lead to meaningful improvement in HF outcomes.⁴ Currently, most eligible patients are not prescribed an SGLT inhibitor at hospital discharge, despite evidence demonstrating benefit and safety for initiating therapy during a hospital admission.⁵ Limitations of the present analysis include that detection of timing of significant benefit is affected by event rate and sample size.

In conclusion, among patients in SCORED, sotagliflozin reduced HF outcomes with significant benefit seen early and sustained throughout the study period.

Sotagliflozin 是一种钠-葡萄糖协同转运蛋白 (SGLT) 1 和 SGLT2 双重抑制剂，可减少患有 2 型糖尿病和心血管 (CV) 高风险的成人患者的心力衰竭 (HF) 结局。 ^{1, 2} 了解治疗的获益时间可以告知处方的紧迫性。

SCORED 是一项针对 2 型糖尿病（糖化血红蛋白≥7%）、慢性肾病（估计肾小球滤过率 25–60 ml/min/1.73 m ² 体表面积）患者的随机、双盲研究区），以及心血管疾病的其他危险因素。 ¹ 患者按 1:1 的比例随机分配至 sotagliflozin 或安慰剂组。主要终点是心血管死亡、心力衰竭住院或心力衰竭紧急就诊的复合终点。次要终点是心力衰竭住院总次数和心力衰竭紧急就诊次数。

在这项事后分析中，从随机化时起连续评估了 sotagliflozin 与安慰剂相比每个结果的风险比 (HR)。确定随机分组后治疗效果达到统计显着性（p < 0.05）并在随访期间保持统计显着性的确切日期。

SCORED 得到了每个试验地点的相关卫生当局、机构审查委员会或伦理委员会的批准。

最终队列由 10 584 名患者组成。该群体的中位年龄为 69 岁，其中女性占 44.9%。中位随访时间为 16.0 个月。在整个研究期间，与安慰剂相比，sotagliflozin 降低了主要终点的风险（HR 0.74；95% 置信区间 [CI] 0.63-0.88；p < 0.001），sotagliflozin 组每 100 人年有 5.6 次事件，安慰剂组每 100 人年发生 7.5 次事件。随机化后 95 天观察到结果持续显着下降（HR 0.70，95% CI 0.50-0.98；图 1A）。

Sotagliflozin 与安慰剂相比，同样降低了次要终点的风险（HR 0.67，95% CI 0.55-0.82；p < 0.001），sotagliflozin 组每 100 人年有 3.5 起事件，而对照组每 100 人年有 5.1 起事件。安慰剂组。随机化后 115 天观察到持续显着降低（HR 0.70，95% CI 0.49–1.00；图 1B）。

在 SCORED 的患者中，sotagliflozin 改善了心力衰竭的结局，随机分组后 95 天即可观察到统计学上显着的改善。这种减少在整个研究期间持续存在。在这些临床稳定的门诊患者中，索格列净的快速临床获益表明立即开始治疗的重要性。早期观察到了有益效果，连续分析表明治疗益处在第一个月达到稳定状态，这可能表明快速的生物学益处（图1）。处方 SGLT 抑制剂治疗的临床惯性可能会导致错过预防心力衰竭事件的机会， ³ 并且快速开始治疗（可能在入院时）可能会导致心力衰竭结局的有意义的改善。 ⁴ 目前，尽管有证据表明在入院期间开始治疗的益处和安全性，但大多数符合条件的患者在出院时并未服用 SGLT 抑制剂。 ⁵ 本分析的局限性包括显着效益时间的检测受到事件发生率和样本大小的影响。

总之，在 SCORED 患者中，sotagliflozin 减少了心力衰竭的结局，并在整个研究期间早期和持续显示出显着的益处。