Sotagliflozin in patients with diabetes and chronic kidney disease.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 m2 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.).
Date Issued
2021-01-14
Date Acceptance
2020-11-01
Citation
New England Journal of Medicine, 2021, 384, pp.129-139
ISSN
0028-4793
Publisher
Massachusetts Medical Society
Start Page
129
End Page
139
Journal / Book Title
New England Journal of Medicine
Volume
384
Copyright Statement
© 2020 Massachusetts Medical Society. All rights reserved.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33200891
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
CARDIOVASCULAR EVENT RATES
SGLT2 INHIBITOR
HEART-FAILURE
RISK
OUTCOMES
OUTPATIENTS
EMPAGLIFLOZIN
SAXAGLIPTIN
MORTALITY
MELLITUS
Aged
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Diabetic Ketoacidosis
Diarrhea
Double-Blind Method
Female
Glycosides
Hospitalization
Humans
Male
Middle Aged
Mycoses
Renal Insufficiency, Chronic
Sodium-Glucose Transporter 1
Sodium-Glucose Transporter 2 Inhibitors
SCORED Investigators
Humans
Mycoses
Cardiovascular Diseases
Diabetic Ketoacidosis
Diabetes Mellitus, Type 2
Diarrhea
Glycosides
Hospitalization
Double-Blind Method
Aged
Middle Aged
Female
Male
Sodium-Glucose Transporter 1
Renal Insufficiency, Chronic
Sodium-Glucose Transporter 2 Inhibitors
General & Internal Medicine
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-11-16