索格列净在伴有慢性肾脏病的糖尿病患者中的应用。
Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease.
机构信息
From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C., B.M.S.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); the State University of New York Downstate School of Public Health, Brooklyn (M.S.); the University of Michigan, Ann Arbor (B.P.); Li Ka Shing Knowledge Institute and the Division of Endocrinology and Metabolism, St. Michael's Hospital, and the Departments of Medicine and Nutritional Sciences, University of Toronto (L.A.L.), and the Division of Nephrology (D.Z.I.C.) and the Cardiovascular Division, Department of Medicine, Women's College Hospital and Peter Munk Cardiac Centre (J.A.U.), University Health Network, University of Toronto - all in Toronto; the University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) - both in Texas; Vanderbilt University Medical Center, Nashville (J.B.L., J.P.D.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); the Section of Endocrinology, Yale School of Medicine, New Haven, CT (S.E.I.); Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City (M.N.K.); the School of Life and Health Sciences, Aston University, Birmingham (C.J.B.), and the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.) - both in the United Kingdom; the Department of Medicine, Estudios Clínicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148, Paris (P.G.S.).
出版信息
N Engl J Med. 2021 Jan 14;384(2):129-139. doi: 10.1056/NEJMoa2030186. Epub 2020 Nov 16.
BACKGROUND
The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied.
METHODS
We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, ≥7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding.
RESULTS
Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo.
CONCLUSIONS
In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo but was associated with adverse events. (Funded by Sanofi and Lexicon Pharmaceuticals; SCORED ClinicalTrials.gov number, NCT03315143.).
背景
钠-葡萄糖共转运蛋白 2 抑制剂（如索格列净）在预防伴有或不伴有白蛋白尿的慢性肾脏病合并糖尿病患者的心血管事件方面的疗效和安全性尚未得到充分研究。
方法
我们开展了一项多中心、双盲试验，将 2 型糖尿病（糖化血红蛋白水平≥7%）、慢性肾脏病（估算肾小球滤过率 25 至 60ml/分钟/1.73m2 ）且存在心血管疾病风险的患者以 1:1 的比例随机分配，接受索格列净或安慰剂治疗。主要终点在试验期间更改为心血管原因死亡、心力衰竭住院和心力衰竭紧急就诊的复合终点。由于资金损失，试验提前结束。
结果
在筛选的 19188 名患者中，有 10584 名患者入组，其中 5292 名患者被分配至索格列净组，5292 名患者被分配至安慰剂组，中位随访时间为 16 个月。索格列净组的主要终点事件发生率为每 100 患者-年 5.6 例，安慰剂组为每 100 患者-年 7.5 例（风险比，0.74；95%置信区间 [CI]，0.63 至 0.88；P<0.001）。每 100 患者-年的心血管原因死亡发生率，索格列净组为 2.2 例，安慰剂组为 2.4 例（风险比，0.90；95%CI，0.73 至 1.12；P=0.35）。对于心血管原因死亡、非致死性心肌梗死或非致死性卒中首次发生的原始复合主要终点，风险比为 0.84（95%CI，0.72 至 0.99）；对于心血管原因死亡或心力衰竭住院的原始复合主要终点，风险比为 0.77（95%CI，0.66 至 0.91）。索格列净组比安慰剂组更常见腹泻、生殖器真菌感染、血容量不足和糖尿病酮症酸中毒。
结论
在伴有或不伴有白蛋白尿的慢性肾脏病合并糖尿病患者中，与安慰剂相比，索格列净可降低心血管原因死亡、心力衰竭住院和心力衰竭紧急就诊复合终点的风险，但与不良事件相关。（由赛诺菲和 Lexicon 制药公司资助；SCORED 临床试验.gov 编号，NCT03315143。）
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