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SGLT1/2 inhibition improves glycemic control and multi-organ protection in type 1 diabetes

Lakshini Yasaswi Herat1, Jennifer Rose Matthews1, Moira Hibbs2

  • 1Dobney Hypertension Centre, School of Biomedical Sciences - Royal Perth Hospital Unit / Royal Perth Hospital Medical Research Foundation, University of Western Australia, Crawley, WA 6009, Australia.

Iscience
|July 31, 2023
PubMed

Insights

Dual SGLT1/2 inhibitors like sotagliflozin improve glycemic control and offer cardiorenal benefits in diabetic mice. This study suggests combined SGLT1/2 inhibition may outperform SGLT2 inhibition for glucose homeostasis and organ protection.

Area of Science:

  • Pharmacology
  • Metabolic Diseases
  • Renal Physiology

Background:

  • Sodium glucose cotransporters (SGLTs) regulate glucose reabsorption.
  • SGLT inhibition is a therapeutic strategy for glycemic control with cardiorenal benefits.
  • Dual SGLT1/2 inhibitors (SGLT1/2i) target both SGLT1 and SGLT2 proteins.

Purpose of the Study:

  • To evaluate the efficacy of the dual SGLT1/2 inhibitor sotagliflozin in a mouse model of diabetes.
  • To assess the metabolic and cardiorenal effects of sotagliflozin treatment.
  • To compare the potential benefits of combined SGLT1/2 inhibition versus SGLT2 inhibition.

Main Methods:

  • Diabetic Akimba mice were treated with sotagliflozin (25 mg/kg/day) or vehicle for 8 weeks.
  • Weekly measurements included urine glucose, water consumption, and body weight.
  • Tissue analysis involved immunohistochemistry and ELISA.

Main Results:

  • Sotagliflozin treatment significantly decreased blood glucose and improved polydipsia in diabetic mice.
  • The drug prevented diabetes-associated mortality.
  • Metabolic benefits and organ protection were observed.

Conclusions:

  • Combined SGLT1/2 inhibition, as exemplified by sotagliflozin, demonstrates significant efficacy in managing diabetes.
  • Sotagliflozin offers potential advantages over SGLT2 inhibitors alone in glucose homeostasis and organ protection.
  • Dual SGLT1/2 inhibition represents a promising therapeutic approach for diabetic complications.
Keywords:
Cell biologyHuman metabolism

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