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

Abstract

Purpose In 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 Results Thus 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. Conclusions The 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.

Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyzer database

“…A network meta-analysis of 14 RCT, including the recent SCORED and SOLOIST trials investigating the effects of sotagliflozin, showed that among gliflozins, sotagliflozin had the greatest effect in lowering risk of stroke [ 27 ]. Thus, larger studies are needed to confirm the effects of SGLT1/SGLT2 inhibition on stroke in type 2 diabetes and to elucidate the potential mechanisms [ 28 ].…”

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction

“…It is also possible that dual SGLT-1 and SGLT-2 inhibition may give a clinical advantage, compared with GLP-1 RA and/or other SGLT-2i, in AMI patients. Indeed, it has been recently demonstrated that the relative increase in SGLT-1 inhibition with sotagliflozin is associated with a greater cardiovascular protection in patients with DM than the currently available SGLT-2i, that provide less degree of SGLT-1 inhibition [ 36 ].…”

Germinated and non-germinated cooked whole millet (Pennisetum glaucum (L.) R. Br.) flours show a promising effect on protein quality, biochemical profile and intestinal health in vivo

“…Although millet consumption was not able to increase the expression of this transporter in our study, recent research indicates that SGLT1 inhibition could be a therapeutic strategy for the management of diabetes, which can be associated with cardiomyopathy. In animal models with type 2 diabetes mellitus 29,[70][71][72] and clinical studies, 73,74 increased SGLT1 intestinal expression is observed in the small intestinal epithelium, which enhances the postprandial hyperglycaemia and its cardiovascular complications. Other studies with caco-2 cells indicate that the phytochemicals, such as polyphenols and tannins, have the capacity to suppress glucose uptake in intestinal cells, by the inhibition of SGLT1.…”