Dual SGLT1 and SGLT2 inhibitor reduces CV outcomes in diabetes patients in two settings

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure – The SOLOIST-WHF trial

Sotagliflozin in patients with diabetes and chronic kidney disease – The SCORED Trial

Presented during the AHA Scientific Sessions 2020 by Deepak Bhatt, Boston, MA, USA.

Introduction and methods

Sotagliflozin is a SGLT2 inhibitor leading to enhanced excretion of glucose in the urine, as well as an inhibitor of SGLT1, resulting in increased glucose elimination in the digestive tract.

The SOLOIST trial examined the effect of sotagliflozin compared to placebo on the primary endpoint of total CV death, hospitalization for HF (HHF) and urgent HF visit in ~1000 patients with diabetes and who were admitted to the hospital with acute decompensated heart failure (ADHF).

The SCORED trial enrolled ~10.000 patients with diabetes and chronic kidney disease who were randomized to sotagliflozin or to placebo. Primary endpoint was the same as in SOLOIST, a composite of total CV death, HHF and urgent HF visit.

Main results

Results of the SOLOIST trial

• Treatment with sotagliflozin resulted in a 33% reduction of the primary endpoint compared to placebo (HR 0.67, 95%CI: 0.52-0.85, P=0.0009). NNT to prevent 1 event was 4.

Results of the SCORED trial

• A 26% reduction of the primary endpoint was observed with sotagliflozin compared to placebo (HR 0.74, 95%CI: 0.63-0.88, P=0.0004). NNT to prevent 1 event was 54. The effect of sotagliflozin was observed early, within 3 months.
• A composite of total CV death, non-fatal MI or non-fatal stroke was reduced by sotagliflozin compared to placebo (HR 0.77, 95%CIL 0.65-0.91, P=0.002).
• Furthermore, endpoints of total fatal or nonfatal MI and endpoint of total fatal or nonfatal stroke were reduced by sotagliflozin compared to placebo (HR 0.68, 95%CI: 0.52-0.89, and HR 0.66, 95%CI: 0.48-0.91, respectively).
• Sotagliflozin resulted in significant HbA1c reduction, even in those with impaired kidney function (eGFR <30 ml/min/1.73²).

Conclusion

The dual SGLT1 and SGLT2 inhibitor sotagliflozin reduced a composite of total CV death, HHF and urgent HF visit compared to placebo in diabetes patients, both the acute setting of ADHF (in SOLOIST) and in a chronic stable patient population of CKD (SCORED).

Prof. Bhatt noted that unlike SGLT2 inhibitor, the SGLT1 inhibition by sotagliflozin provided glycemic control even at the lower range of eGFR. Furthermore, the decrease in MI and stroke by sotagliflozin suggests a relative early anti-atherosclerotic effect by SGLT1 inhibition, requiring further exploration, said Bhatt.

Discussion

The discussant Jane Wilcox, MD (Chicago, IL, USA) asked where the results of SCORED fit in with regard to the previous SGLT2i trials. Most previous CVOTs with SGLT2i demonstrated reduction in HF events, as opposed to atherosclerotic events. In the SCORED, both HF and atherosclerotic events (CV death, stroke and MI) seem to be affected. A pooled analysis of SOLOIST and SCORED showed a 37% reduction of CV death and HF outcomes in HF patients with preserved ejection fraction. Wilcox said the implications of sotagliflozin are really clear, it adds to the SGLT2i story among diabetes patients.

- Our reporting is based on the information during AHA Scientific Sessions 2020 -

The findings of the SOLOIST study were simultaneously published in N Eng J Med The findings of the SCORED study were simultaneously published in N Eng J Med