Sotagliflozin and Kidney Outcomes, Kidney Function, and Albuminuria in Type 2 Diabetes and CKD: A Secondary Analysis of the SCORED Trial

Clin J Am Soc Nephrol. 2024 May 1;19(5):557-564. doi: 10.2215/CJN.0000000000000414. Epub 2024 Jan 26.

Abstract

Background: In the initial analysis of the Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial, because of early trial termination and suspension of adjudication, reconciliation of eGFR laboratory data and case report forms had not been completed. This resulted in a small number of kidney composite events and a nominal effect of sotagliflozin versus placebo on this outcome. This exploratory analysis uses laboratory eGFR data, regardless of case report form completion, to assess the effects of sotagliflozin on the predefined kidney composite end point in the SCORED trial and additional cardiorenal composite end points.

Methods: SCORED was a multicenter, randomized trial evaluating cardiorenal outcomes with sotagliflozin versus placebo in 10,584 patients with type 2 diabetes and CKD. This exploratory analysis used laboratory data to derive the eGFR components and case report form data for the non-laboratory-defined components that together made up the kidney and cardiorenal composites. AKI was also assessed in this dataset.

Results: Using laboratory data, 223 events were identified, and sotagliflozin reduced the risk of the composite of first event of sustained ≥50% decline in eGFR, eGFR <15 ml/min per 1.73 m 2 , dialysis, or kidney transplant with 87 events (1.6%) in the sotagliflozin group and 136 events (2.6%) in the placebo group (hazard ratio [95% confidence interval], 0.62 [0.48 to 0.82]), P < 0.001). Sotagliflozin reduced the risk of a cardiorenal composite end point defined as the abovementioned composite plus cardiovascular or kidney death with 239 events (4.5%) in the sotagliflozin group and 306 events (5.7%) in the placebo group (hazard ratio [95% confidence interval], 0.77 [0.65 to 0.91], P = 0.0023). The results were consistent when using different eGFR decline thresholds and when only including kidney death in composites (all P < 0.01). The incidence of AKI was similar between treatment groups.

Conclusions: In this exploratory analysis using the complete laboratory dataset, sotagliflozin reduced the risk of kidney and cardiorenal composite end points in patients with type 2 diabetes and CKD.

Clinical trial registry name and registration number: ClinicalTrials.gov Identifier: NCT03315143 .

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Multicenter Study

MeSH terms

  • Aged
  • Albuminuria*
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / mortality
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / physiopathology
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate* / drug effects
  • Glycosides* / adverse effects
  • Glycosides* / therapeutic use
  • Humans
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / mortality
  • Renal Insufficiency, Chronic* / physiopathology
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Glycosides
  • (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
  • Sodium-Glucose Transporter 2 Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03315143