The Gut Microbiota-Related Antihyperglycemic Effect of Metformin

It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the fi...

Full description

Saved in:
Bibliographic Details
Main Authors: Izabela Szymczak-Pajor, Józef Drzewoski, Małgorzata Kozłowska, Jan Krekora, Agnieszka Śliwińska
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/18/1/55
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832587736579571712
author Izabela Szymczak-Pajor
Józef Drzewoski
Małgorzata Kozłowska
Jan Krekora
Agnieszka Śliwińska
author_facet Izabela Szymczak-Pajor
Józef Drzewoski
Małgorzata Kozłowska
Jan Krekora
Agnieszka Śliwińska
author_sort Izabela Szymczak-Pajor
collection DOAJ
description It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut.
format Article
id doaj-art-c37d4ec8d77242c9943bccb911e224c9
institution Kabale University
issn 1424-8247
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj-art-c37d4ec8d77242c9943bccb911e224c92025-01-24T13:45:12ZengMDPI AGPharmaceuticals1424-82472025-01-011815510.3390/ph18010055The Gut Microbiota-Related Antihyperglycemic Effect of MetforminIzabela Szymczak-Pajor0Józef Drzewoski1Małgorzata Kozłowska2Jan Krekora3Agnieszka Śliwińska4Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandCentral Teaching Hospital of the Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandDepartment of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandCentral Teaching Hospital of the Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandDepartment of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, PolandIt is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut.https://www.mdpi.com/1424-8247/18/1/55glucose-lowering effectinsulin resistance (IR)metforminmicrobiotatype 2 diabetes mellitus (T2DM)
spellingShingle Izabela Szymczak-Pajor
Józef Drzewoski
Małgorzata Kozłowska
Jan Krekora
Agnieszka Śliwińska
The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
Pharmaceuticals
glucose-lowering effect
insulin resistance (IR)
metformin
microbiota
type 2 diabetes mellitus (T2DM)
title The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
title_full The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
title_fullStr The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
title_full_unstemmed The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
title_short The Gut Microbiota-Related Antihyperglycemic Effect of Metformin
title_sort gut microbiota related antihyperglycemic effect of metformin
topic glucose-lowering effect
insulin resistance (IR)
metformin
microbiota
type 2 diabetes mellitus (T2DM)
url https://www.mdpi.com/1424-8247/18/1/55
work_keys_str_mv AT izabelaszymczakpajor thegutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT jozefdrzewoski thegutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT małgorzatakozłowska thegutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT jankrekora thegutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT agnieszkasliwinska thegutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT izabelaszymczakpajor gutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT jozefdrzewoski gutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT małgorzatakozłowska gutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT jankrekora gutmicrobiotarelatedantihyperglycemiceffectofmetformin
AT agnieszkasliwinska gutmicrobiotarelatedantihyperglycemiceffectofmetformin