Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease

Abstract

BACKGROUNDThe 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. METHODSWe 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 2 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. RESULTSOf 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. CONCLUSIONSIn 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.

Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis

“…Finally, thirteen studies published up to November 20, 2020, were selected for our meta-analysis according to the inclusion criteria [12,[28][29][30][31][32][33][34][35][36][37][38][39]. Out of thirteen studies, six studies were RCTs that compared SGLT-2 inhibitors (Canagliflozin [12,29], Dapagliflozin [31], Empagliflozin [30], Ertugliflozin [28], and Sotagliflozin [32]) with placebo; seven studies compared GLP-1 RAs (Albiglutide [34], Dulaglutide weekly [33], Exenatide weekly [35], Liraglutide [37], Lixisenatide [39], Semaglutide subcutaneously weekly [38], and Semaglutide oral [36]) with placebo. The pooled population consisted of 20,106 patients in SGLT-2 inhibitor studies (10,716 in the group treated with SGLT-2 inhibitors and 9390 in the control group) and 12,843 patients in GLP-1 RA studies (6364 in the group treated with GLP-1 RAs and 6479 in the control group).…”

Cardiovascular and Renal Outcomes with SGLT-2 Inhibitors versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Network Meta-analysis

“…Hemoglobin A1c ranged from 6.5% to 12%. eGFR ranged from 15 to 59 ml/min/1.73m 2 in one study [33], 25 to 59 ml/min/1.73m 2 in one study, [32] and from 30 to 59 ml/min/1.73m 2 in other studies, with two studies that not mentioned their lower limit [31,38]. The median length of follow-up ranged from 16.0 months to 50.4 months in SGLT-2 inhibitor studies and 19.2 months to 64.8 months in GLP-1 RA studies.…”

“…Finally, thirteen studies published up to November 20, 2020, were selected for our meta-analysis according to the inclusion criteria. [12,[28][29][30][31][32][33][34][35][36][37][38][39] Out of thirteen studies, six studies were RCTs that compared SGLT-2 inhibitors (Canagli ozin, [12,29] Dapagli ozin, [31] Empagli ozin, [30] Ertugli ozin [28], and Sotagli ozin [32]) with placebo; seven studies compared GLP-1 RAs (Albiglutide, [34] Dulaglutide weekly, [33] Exenatide weekly, [35] Liraglutide, [37] Lixisenatide, [39] Semaglutide subcutaneously weekly, [38] and Semaglutide oral [36]) with placebo. The pooled population consisted of 20,106 patients in SGLT-2 inhibitor studies (10,716 in the group treated with SGLT-2 inhibitors and 9,390 in the control group) and 12,843 patients in GLP-1 RA studies (6,364 in the group treated with GLP-1 RAs and 6,479 in the control group).…”

Lo mejor del 2020: Estudios que marcarán nuestra práctica clínica

“…Con un efecto similar, la Sotaglifozina, droga que actúa como iSGLT2 y iSGLT1 en pacientes con diabetes mellitus (DM) tipo 1 (inhibe la absorción de glucosa a nivel del túbulo renal proximal y a nivel intestinal) amplia su campo de estudio en SOLOIST-WHF (10) y SCORED (11) que pese a haber sido detenidos por la pandemia, demostraron su eficacia en población con DM2. SOLOIST-WHF (10) aleatorizó a una población hospitalizada por IC, estables o a menos de tres días de su egreso por IC, con NT-proBNP≥600 (≥1800 si fibrilación auricular) y DM2, al uso de sotaglifozina 200 mg (con un incremento a 400 mg si no efectos adversos) vs placebo.…”

“…El beneficio se logró en una media de 9 meses en el evento primario compuesto de muerte CV y hospitalización por IC y visitas a urgencia por IC con una ↓ RA de 25 eventos por 100 pacientes/año, y un NNT=4 pacientes/ año, con una respuesta beneficiosa significativa desde el día 28 de iniciado el medicamento; los efectos adversos más frecuentes encontrados fueron diarrea e hipoglicemia. SCORED (11) estudió a una población con DM2, ERC (TFG: 25-60 mL/min/1,73m 2 ) y factor de riesgo CV, logrando el mismo beneficio en evento primario compuesto que SOLOIST-WHF en un seguimiento a 16 meses con una ↓ RA de 1,9%, NNT=54, beneficio también observado tempranamente (tres meses). Además, dentro de los objetivos secundarios se obtiene un beneficio significativo en infarto de miocardio (IM) y evento cerebrovascular (EVC) tanto fatal como no fatal, llevando a la hipótesis del posible efecto antiisquémico de los iSGLT1.…”