The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus

Gabriel Steg,Lawrence A. Leiter,Bertram Pitt,Deepak L. Bhatt

doi:10.1007/s10557-021-07291-y

Abstract

PurposeIn patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings.Methods and ResultsThus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding.ConclusionsThe role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.

Highlights

In patients with type 2 diabetes mellitus, both sodiumglucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have been shown to significantly improve cardiovascular and kidney outcomes independent of their effect on glycemia
The recent findings from the SCORED (10,584 patients with type 2 diabetes and Chronic kidney disease (CKD) randomized to sotagliflozin or placebo) and SOLOIST (1222 patients with type 2 diabetes admitted with worsening heart failure randomized to sotagliflozin or placebo) trials suggest that like SGLT2is, SGLT1/2 s reduce the composite of deaths from cardiovascular causes, hospitalization for heart failure, and urgent visits for heart failure but may provide greater reduction in myocardial infarction (MI) and stroke [5, 6]
This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of MI and stroke in patients with type 2 diabetes and further postulate mechanisms associated with SGLT1 inhibition that could account for these findings

Summary

Introduction

In patients with type 2 diabetes mellitus, both sodiumglucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have been shown to significantly improve cardiovascular and kidney outcomes independent of their effect on glycemia. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of MI and stroke in patients with type 2 diabetes and further postulate mechanisms associated with SGLT1 inhibition that could account for these findings.

Results

Conclusion