Study Summary

The SCORED and SOLOIST-WHF trials showed a beneficial effect of sotagliflozin (a sodium-glucose cotransporter [SGLT]-1 and -2 inhibitor) on cardiovascular outcomes among patients with type 2 diabetes (T2D) and chronic kidney disease (in SCORED), and among patients with T2D and heart failure (HF) (in SOLOIST-WHF). The pooled data from the SCORED and SOLOIST-WHF trials (N = 11,784) showed favorable effects of sotagliflozin in reduction of the composite primary end point of total cardiovascular deaths, hospitalizations for HF, and urgent visits for HF across the full range of ejection fractions (EFs), including in patients with HF with preserved EF (HFpEF) (see accompanying Hurst’s Central Illustration). At 24 months follow-up, total primary end point events for sotagliflozin versus placebo were 15.5 versus 21.1 per 100 patient-years (HR 0.72, 95% CI 0.63-0.82; P = 0.000002). The benefits of treatment were noted in males and females. Among patients with HFpEF (EF ≥50%, N = 739), the rates of primary end point events per 100 patient-years for sotagliflozin versus placebo were 37.5 versus 59.0 (HR 0.63, 95% CI 0.45-0.89; P = 0.009).

Commentary

Study Strengths: SCORED and SOLOIST-WHF were large, multicenter, randomized, double-blinded, placebo-controlled trials. The pooled analysis examined data from 11,784 patients and is the first to show benefit of an agent in treatment of patients with T2D and HFpEF (DELIVER and EMPEROR-Preserved trials are currently ongoing). The observation of beneficial effect of sotagliflozin in both males and females is an additional value of this study.

Study Limitations: These two trials ended early owing to the loss of funding due to the COVID-19 pandemic. Early termination limited the statistical power to detect significant reductions in certain end points. Some of the analyses were prespecified and others were post hoc. Finally, racial groups other than Caucasian were under-represented in both studies.

Next Steps/Clinical Perspectives: While both SGLT 1 and 2 contribute to the renal absorption of glucose, SGLT1 is the main transporter for absorption of glucose and galactose in the gastrointestinal system. The role of SGLT inhibitors in the management of patients with HFpEF is being investigated in DELIVER (with dapagliflozin) and EMPEROR-Preserved (with empagliflozin). If these trials confirm the beneficial effect of SGLT inhibitors in this group of patients, the next step would be to directly compare SGLT-1 and -2 versus SGLT-2 inhibitors.

Trial References

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Benefits of sodium glucose co-transporter-1/2 inhibition with sotagliflozin across the full spectrum of ejection fraction, including heart failure with preserved ejection fraction. Presented by Dr. Deepak Bhatt at the American College of Cardiology 2021 Scientific Sessions, May 17, 2021.
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Bhatt  DL, Szarek  M, Steg  PG,  et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. doi: 10.1056/NEJMoa2030183.
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Bhatt  DL, Szarek  M, Pitt  B,  et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. doi: 10.1056/NEJMoa2030186