Sotagliflozin in Heart Failure and Diabetes

According to research presented by Dr. Deepak Bhatt from the Brigham and Women’s Hospital Heart and Vascular Center, treatment with sotagliflozin significantly lowered total deaths and hospitalizations in patients with diabetes and worsening heart failure

Heart failure is a chronic condition where the heart’s muscles are unable to pump enough blood throughout the body effectively. The heart may attempt to compensate by enlarging, developing more muscle mass, or pumping faster. The heart will continue to try to compensate until these processes no longer work. Symptoms such as shortness of breath, coughing, fatigue, and impaired thinking may arise when this happens.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially used to treat hyperglycemia in patients with type 2 diabetes. It was later found out that specific SGLT2 inhibitors lower the risk of heart failure hospitalizations and death from cardiovascular causes. Though several positive aspects come from SGLT2 inhibitors, the safety of use after decompensated heart failure needs further research. These points led to the construction of this trial referred to as the SOLOIST-WHF trial. The name comes from the full title, the Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure trial.

This trial sought to determine that sotagliflozin would decrease the risk of death from cardiovascular issues, hospitalizations from heart failure, and urgent care visits among patients with diabetes and worsening heart failure in reduced and preserved ejection fraction. Dr. Bhatt and his colleagues submitted this research to the New England Journal of Medicine to examine and summarize the benefits of sotagliflozin in this patient population. Sotagliflozin is an SGLT2 inhibitor that also possesses some qualities of SGLT1 inhibition. SGLT2 inhibition causes more glucose to be excreted through the urine, while SGLT1 inhibition reduces glucose levels after meals by delaying glucose absorption. The authors, sponsored by Lexicon Pharmaceuticals, used a double-blind, randomized, placebo-controlled approach in this trial. A total amount of 4000 patients were screened, while 1222 were included in the statistical analysis. Six hundred eight patients were randomly assigned to the treatment group, and 614 patients were added to the control group. The first patient was introduced into this study in June 2018, while the last was in March 2020. Eligible patients included those who were 18 to 85 years old. Patients also had to have been hospitalized due to heart failure and have a previous diagnosis of type 2 diabetes. Exclusion criteria for this trial included previous stroke, coronary artery bypass surgery, and end-stage heart failure. The primary outcome for this study was the total number of deaths from cardiovascular events, hospitalizations, and urgent visits due to heart failure. The secondary outcomes included the total number of hospitalizations and urgent visits for heart failure, number of deaths from any cause, nonfatal heart attacks, and nonfatal strokes.

The results from this study showed that patients with type 2 diabetes who received sotagliflozin had a lower risk of primary outcomes such as cardiovascular issues, hospitalizations, and urgent care visits in patients with worsening heart failure. With regard to the primary outcomes, they occurred in 51.0 per 100 patients in the treatment group as opposed to 76.3 per 100 patients in the control group. The secondary outcomes were consistent with the results obtained from the primary analysis. The incidence of death from any cause also did not differ between both groups.

In conclusion, SGLT2 inhibitors have many benefits to use in patients with diabetes and worsening heart failure. As stated by Dr. Bhatt, initiating sotagliflozin led to benefits, including fewer occurrences of cardiovascular-related deaths, hospitalizations, and urgent visits. Other benefits include weight loss, cellular reprogramming, lower blood pressure, and left ventricular hypertrophy. Limitations of this trial include a loss of funding which had an impact on the planned sample size. This also affected the statistical power behind the results of this study.

Practice Pearls:

• Heart failure is a chronic condition where the heart’s muscles are unable to effectively pump enough blood throughout the body.
• Sodium-glucose cotransporter two inhibitors were initially used to treat hyperglycemia in patients with type 2 diabetes.
• The results from this study suggest that patients with type 2 diabetes who received sotagliflozin had a lower risk of primary outcomes such as cardiovascular issues, hospitalizations, and urgent care visits in patients with worsening heart failure.

References

Bhatt, Deepak L., et al. “Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.” New England Journal of Medicine, vol. 384, no. 2, 2021, pp. 117–128., link

“What Is Heart Failure?” Www.heart.org, link

Kmeone Kingdom, MPH, PharmD Candidate, South College School of Pharmacy