SCORED, SOLOIST Trials to Add to Evidence for Treating Diabetes with SGLT2 Inhibitors

Two large clinical trials conducted by investigators at Brigham and Women’s Hospital add new evidence about the benefits for patients with diabetes and chronic kidney disease and those with diabetes or recent worsening heart failure. Previous studies have tried to show better blood glucose control, cardiovascular benefits, weight loss, and more for patients with diabetes taking sodium/glucose cotransporter 2 (SGLT2) inhibitors.

The two paired trials evaluated sotagliflozin, a drug that inhibits SGLT2 and SGLT1, according to a study published in The New England Journal of Medicine.

“With the results of these large two 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,” said Deepak L. Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programs at the Brigham, in a press release.

Bhatt added that the “Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk” (SCORED) trial 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. Meanwhile, “The Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure” (SOLOIST-WHF) trial 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.

Further, sotagliflozin inhibits not only SGLT2, but also SGLT1. SGLT2 inhibition helps the body eliminate blood sugar via urine, whereas SGLT1 inhibition leads to blood sugar reduction via the digestive tract.

In the SCORED trial, investigators evaluated whether sotagliflozin could prevent cardiovascular events in patients with diabetes with chronic kidney disease. The trial enrolled 10,584 patients who were followed for an average of 16 months but ended early due to the coronavirus disease 2019 (COVID-19)-related loss of funding. The study authors changed the primary endpoint, but the initial endpoint reached statistical significance.

Unlike previous trials, SCORED enrolled patients across the full range of albuminuria, or leakage of protein into the urine that can happen when a person has diabetes. Further, sotagliflozin significantly reduced the primary endpoint of total occurrences of cardiovascular deaths, hospitalizations for heart failure, or urgent visits for heart failure regardless of the patient’s degree of albuminuria by approximately 26%.

In addition, sotagliflozin reduced the rate of cardiovascular death, myocardial infarction, or stroke, with an early benefit potentially mediated by the SGLT1 action. There was a reduction in the total number of fatal or non-fatal heart attacks and the total number of fatal or non-fatal strokes by 32% and 34%, respectively.

“SCORED is the first trial to show the benefits of SGLT2 inhibitors across the full range of albuminuria,” Bhatt said in a press release. “It is also the first trial of an SGLT2 inhibitor to show a beneficial effect on stroke.”

In the “The Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure” (SOLOIST-WHF) trial, 1222 patients with type 2 diabetes mellitus and recent worsening heart failure requiring hospitalization were enrolled. The patients were randomized to sotagliflozin or placebo and followed for an average of 9 months, but the trial ended early due to loss of funding from the COVID-19 pandemic.

Data from the patients who took part in the trial showed a significant 33% reduction in the study’s primary endpoint (defined as the total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure) for patients with either heart failure with reduced or preserved ejection fraction. Taking the drug prior to hospital discharge was safe and effective.

“SOLOIST is the first large, randomized trial to show the safety and efficacy of SGLT2 inhibitors when initiated in patients hospitalized with acute heart failure,” Bhatt said in a press release. “Thus, it really changes the field and supports early initiation of this class of drugs.”

There were limitations of the SCORED and SOLOIST trials, including premature cessation due to loss of funding that led to an inability to complete the intended duration of follow-up. However, both trials found statistically significant declines in rates of total cardiovascular events for their respective patient populations.

REFERENCE

SCORED and SOLOIST trials add to evidence for treating diabetes with SGLT2 inhibitors. Brigham Health and Women’s Hospital. https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=3732. Published November 16, 2020. Accessed February 3, 2021.