Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives

Cardiovasc Diabetol. 2019 Feb 28;18(1):20. doi: 10.1186/s12933-019-0828-y.

Abstract

Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities.

Keywords: Diabetes; Hypoglycemic therapy; SGLT2 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Glycosides / adverse effects
  • Glycosides / therapeutic use*
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Glucose Transporter 2 / drug effects*
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycosides
  • SLC5A1 protein, human
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Associated data

  • ClinicalTrials.gov/NCT03315143