Sotagliflozin as a potential treatment for type 2 diabetes mellitus
Abstract
INTRODUCTION: SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM). AREAS COVERED: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. Original publications in English were selected as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database. EXPERT OPINION: By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secretion, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. While sotagliflozin was first assessed in T2DM, it is now in phase 3 development as an adjuvant treatment in patients with T1DM after positive results from a pilot study.
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Sotagliflozin acts beyond renal SGLT-2 inhibition to induce partial inhibition of intestinal SGLT-1, leading to augmented GLP-1 and insulin secretion and reduced postprandial glucose excursions.
“This is particularly true for first-in-class examples, such as the dual SGLT-1/SGLT-2 inhibitor sotagliflozin, which has lower selectivity for SGLT-2 and acts beyond inhibition of renal glucose reabsorption by SGLT-2 to induce partial inhibition of intestinal SGLT-1, leading to augmented GLP-1 and insulin secretion, and a reduction in postprandial glucose excursions (75).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [75]
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“This is particularly true for first-in-class examples, such as the dual SGLT-1/SGLT-2 inhibitor sotagliflozin, which has lower selectivity for SGLT-2 and acts beyond inhibition of renal glucose reabsorption by SGLT-2 to induce partial inhibition of intestinal SGLT-1, leading to augmented GLP-1 and insulin secretion, a…”
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Turning Foes to Friends: Knocking Down Diabetes Associated SGLT2 Transporters and Sustaining Life
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Inhibition of SGLT1: The Alternative Way Toward Incretin Protection
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- Authors
- Cariou, B., & Charbonnel, B.
- Affiliations
- Inserm (FR)
- Université de Nantes (FR)
- Corresponding author
- Cariou, Bertrand
- Venue
- Expert Opinion on Investigational Drugs
- Publisher
- Informa Healthcare
- Published
- 2015-11-07
- Volume
- 24
- Issue
- 12
- Pages
- 1647-1656
- ISSN
- 1354-3784 (ISSN-L)
- 1744-7658
- OpenAlex
- W2115247225
- Semantic Scholar
- 8d31a77f3f25c8e20cf2c850c9a6b04bb517542e
- Cited by
- 37
- References
- 56
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2020: 2 · 2019: 3 · 2018: 11 · 2017: 6 · 2016: 4
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Investigational Drugs (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- sotagliflozin, type 2 diabetes, SGLT1 inhibition, SGLT2 inhibition, intestinal glucose absorption, urinary glucose excretion, postprandial blood glucose, GLP-1 secretion, HbA1c reduction, oral antidiabetic drugs
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Insulin Secretion, Animals, Diabetes Mellitus, Type 2, Glucose, Glycosides, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Sodium-Glucose Transporter 1
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