Although both trials ended early due to the COVID-19-related loss of funding, data from 2 large clinical trials showed new benefits of taking sotagliflozin for patients with diabetes and chronic kidney disease as well as those with diabetes and recent worsening heart failure.
Prof. Deepak Bhatt (Brigham and Women’s Hospital, USA) presented the 4,000-patient SOLOIST-WHF trial, as well as the 10,584-patient, SCORED trial, both of which tested the dual sodium-glucose cotransporter-1 and -2 (SGLT1/SGLT2) inhibitor sotagliflozin, in a late-breaking session [1,2]. Both trials were simultaneously published in the New England Journal of Medicine [3,4]. Both studies were prematurely closed because of COVID-19. SCORED was fully enrolled but with an abbreviated follow-up period, and the smaller SOLOIST-WHF study only randomized about a third of their planned enrolment numbers.
SOLOIST-WHF was a multicentre, randomized, double-blinded, placebo-controlled phase 3 study evaluating the cardiovascular efficacy of 200 mg sotagliflozin once daily versus placebo when added to standard of care in 1,222 patients with type 2 diabetes who had recently been hospitalized for worsening heart failure (HF).
The primary endpoint of SOLOIST-WHF was met; the total number of events comprised of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure in patients starting treatment within 3 days of hospital discharge. There were 51.0 primary endpoint events per 100 patient-years in the sotagliflozin treated group as compared with 76.3 events per 100 patient-years in the placebo group (HR 0.67; 95% CI 0.52-0.85; P<0.001). There were 10.6 events of cardiovascular death per 100 patient-years in the sotagliflozin treated group as compared with 12.5 events per 100 patient-years in the placebo group (HR 0.84; 95% CI 0.58-1.22; P=0.36). The results for the first occurrence of cardiovascular death or hospitalization for heart failure based on investigator reported events were consistent with those of the modified primary endpoint (HR 0.71; 95% CI 0.57-0.89; P=0.003).
SCORED was a multicentre, randomized, double-blinded, placebo-controlled phase 3 study evaluating the cardiovascular efficacy of sotagliflozin versus placebo when added to standard of care in 10,584 patients with type 2 diabetes, chronic kidney disease with an eGFR of 25-60 ml/minute/1.73 m² of body-surface area, and risks for cardiovascular disease. The primary endpoint was the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure in patients treated with sotagliflozin compared with placebo. The initial dose of 200 mg once daily of sotagliflozin was increased to 400 mg once daily if side effects were manageable.
Again, the primary endpoint was met; sotagliflozin resulted in a significantly lower total number of cardiovascular deaths, heart failure hospitalizations, and urgent visits as compared with placebo. There were 5.6 primary endpoint events per 100 patient-years in the sotagliflozin treated group as compared with 7.5 events per 100 patient-years in the placebo group (HR 0.74; 95% CI 0.63-0.88; P<0.001). There were 2.2 events of cardiovascular death per 100 patient-years in the sotagliflozin treated group as compared to 2.4 events per 100 patient-years in the placebo group (HR 0.90; 95% CI 0.73-1.12; P=0.35).
There was also an average reduction in hemoglobin A1c of 0.56% in the sotagliflozin arm as compared with a reduction of 0.25% in the placebo group in patients with eGFR <30 ml/minute/1.73 m² of body-surface area (P<0.001). In patients with eGFR ≥30 ml/minute/1.73 m², haemoglobin A1c was 0.60% lower in the sotagliflozin arm versus 0.17% lowering the placebo group (P<0.001).
Prof. Bhatt concluded: “With the results of these two large trials, adding to other recent data about drugs in this class, it is now clear that most patients with type 2 diabetes and either kidney disease or heart failure should be on an SGLT2 inhibitor. SCORED provides further randomized clinical trial evidence that SGLT2 inhibitors should be part of the standard of care for patients with type 2 diabetes mellitus and kidney disease. And SOLOIST demonstrates that early, in-hospital initiation of SGLT2 inhibitors is safe, effective, and should become the standard of care in patients with type 2 diabetes mellitus and heart failure.”
- Bhatt D, et al. Sotagliflozin in Diabetes Patients with Recent Worsening Heart Failure – SOLOIST-WHF. LBS.07. Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Bhatt D, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease – SCORED. Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Bhatt D, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. New Engl J Med 2020; Nov DOI:10.1056/NEJMoa2030183.
- Bhatt D, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. New Engl J Med 2020; Nov 16. DOI:1056/NEJMoa2030186.
