# SGLT1 and SGLT2 Modulation in Antidiabetic Therapy—Comparative Insights into Gliflozins and Natural Compounds Resveratrol and Viniferin

## TL;DR

This paper reviews how synthetic and natural compounds, including resveratrol and viniferin, affect glucose transporters to manage diabetes.

## Contribution

The paper provides a comparative analysis of gliflozins and natural compounds like resveratrol and viniferin in modulating SGLT1 and SGLT2.

## Key findings

- Resveratrol shows high cellular uptake and metabolic conversion, while ε-viniferin has poor intestinal permeability.
- Gliflozins are effective dual SGLT1/SGLT2 inhibitors with proven clinical benefits.
- Natural stilbenoids like resveratrol and viniferin show in vitro promise but lack sufficient in vivo and clinical data.

## Abstract

Glucose transport dysregulation plays a central role in pathophysiology of diabetes mellitus. Synthetic agents like sotagliflozin or canagliflozin have been discovered recently and are currently used as antidiabetic therapy, providing great efficacy in modulation of glucose transport. However, the search for additional compounds with antidiabetic potential continues, as researchers aim to identify new molecules that may complement or enhance existing therapies. Numerous plant-derived compounds are currently under investigation and have demonstrated promising effects, while others remain far less studied yet could hold meaningful potential. In this context, resveratrol and its oligomers, including ε-viniferin, have gained attention due to promising in vitro findings, particularly due to influencing glucose homeostasis through direct SGLT interaction, indirect metabolic pathways, or a combination of both. This review examines their molecular mechanisms, absorption profiles, and inhibitory activity on sodium–glucose cotransporters SGLT1 and SGLT2. While resveratrol demonstrates high cellular uptake and metabolic conversion, ε-viniferin exhibits poor intestinal permeability, suggesting limited systemic bioavailability but potential local activity at the intestinal epithelium. Gliflozins are clinically validated dual SGLT1/SGLT2 inhibitors that offer superior glucose-lowering efficacy and organ protection. In regard to stilbenoids, they offer promising in vitro results, though in vivo studies and clinical trials are scarce. Understanding resveratrol and viniferin pharmacokinetics, target interactions, and limitations is vital for their development as potential complementary or even alternative antidiabetic therapies.