New data presented at the Scientific Sessions from two recent clinical trials of sotagliflozin, the first dual sodium-glucose cotransporter-1 (SGLT1) and SGLT2 inhibitor in phase 3 randomized controlled clinical trials, showed significant cardiovascular (CV) benefits in patients with type 2 diabetes and heart failure (HF) and other CV conditions.
Initial results 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) and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trials were published in the New England Journal of Medicine in January 2021.
Researchers presented new data from the trials on Tuesday, June 29, during the symposium Update on SCORED and SOLOIST Cardiovascular and Kidney Outcomes Trials. The session can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.
A meta-analysis of the two trials with a total of 11,784 patients showed a hazard ratio of 0.72 favoring sotagliflozin over placebo for total cardiovascular death, hospitalization for HF, and urgent HF visit. The HF benefit was consistent across the range of reduced to preserved ejection fraction (EF).
“We now know that sotagliflozin produces very large benefits in patients with reduced ejection fraction and preserved ejection fraction,” said Deepak Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart and Vascular Center, and Professor of Medicine, Harvard Medical School. “Among older women in particular, HFpEF (heart failure with preserved ejection fraction) is a challenging issue to treat. It appears there is now a therapy that is effective.”
Dr. Bhatt chaired the SCORED executive committee. Both SCORED and SOLOIST-WHF were terminated early due to funding difficulties exacerbated by the COVID-19 pandemic. Trial protocols were amended to allow for the early termination.
SGLT2 is active primarily in the kidney, blocking reabsorption of glucose, and requires kidney function. SGLT1 is the primary transporter for glucose and galactose in the gastrointestinal tract and does not depend on kidney function.
SOLOIST-WHF enrolled 1,222 patients (out of a planned 4,000) hospitalized for heart failure about to be discharged, or who had been discharged within the past three days. All had type 2 diabetes. The planned primary endpoint was time to the first occurrence of cardiovascular death or hospitalized heart failure.
The trial was halted in August 2020 with all patients and data still blinded. The primary endpoint was changed to a composite of CV death, hospitalization for HF, or urgent HF visit. The median follow-up was nine months.
SOLOIST-WHF showed a hazard ratio of 0.67 favoring sotagliflozin (p=0.0009) versus placebo.
“The curves showed very early separation,” reported Subodh Verma, MD, PhD, FRCSC, Professor of Medicine, University of Toronto, and Canada Research Chair in Cardiovascular Surgery at St. Michael’s Hospital, Toronto. “The p value achieved statistical significance within 28 days of starting treatment.”
SCORED enrolled patients with chronic kidney disease and an estimated glomerular filtration rate (eGFR) between 25 and 59 who also had type 2 diabetes and CV risk factors. The trial was fully enrolled with 10,584 patients before it was terminated.
The original co-primary endpoints—time to first major adverse cardiac event and time to first death from CV causes or hospitalization for heart failure—were changed to a composite of total CV deaths, hospitalizations for HF, and urgent HF visits. The median follow-up was 15.9 months.
The trial showed a hazard ratio of 0.74 favoring sotagliflozin (p=0.0004) versus placebo.
“The benefit of sotagliflozin became significant after 95 days,” said Mikhail N. Kosiborod, MD, Vice President of Research, Saint Luke’s Health System, and Professor of Medicine, University of Missouri–Kansas City. “Cardiovascular death was numerically reduced, driven mostly by heart failure improvement, but did not reach statistical significance.”
A numerical trend toward renal protection did not reach statistical significance, likely due to early termination.
“Only 89 renal events occurred in the shortened duration, but there is a suggestion of benefit in acute kidney injury,” noted Julia B. Lewis, MD, Professor of Medicine, Vanderbilt University Medical Center. “Early eGFR changes seen in the sotagliflozin group are consistent with other interventions that preserve renal function.”