PMID- 37188578
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20240326
IS  - 1873-3735 (Electronic)
IS  - 0165-6147 (Linking)
VI  - 44
IP  - 7
DP  - 2023 Jul
TI  - Striking a gut-liver balance for the antidiabetic effects of metformin.
PG  - 457-473
LID - S0165-6147(23)00087-1 [pii]
LID - 10.1016/j.tips.2023.04.004 [doi]
AB  - Metformin is the most prescribed drug for the treatment of type 2 diabetes 
      mellitus (T2DM), but its mechanism of action has not yet been completely 
      elucidated. Classically, the liver has been considered the major site of action 
      of metformin. However, over the past few years, advances have unveiled the gut as 
      an additional important target of metformin, which contributes to its 
      glucose-lowering effect through new mechanisms of action. A better understanding 
      of the mechanistic details of metformin action in the gut and the liver and its 
      relevance in patients remains the challenge of present and future research and 
      may impact drug development for the treatment of T2DM. Here, we offer a critical 
      analysis of the current status of metformin-driven multiorgan glucose-lowering 
      effects.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Barroso, Emma
AU  - Barroso E
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of 
      Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of 
      the University of Barcelona (IBUB), Barcelona, Spain; Pediatric Research 
      Institute-Hospital Sant Joan de Deu, E-08950 Barcelona, Spain; CIBER de Diabetes 
      y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Avinguda 
      Joan XXII 27-31, E-08028 Barcelona, Spain.
FAU - Montori-Grau, Marta
AU  - Montori-Grau M
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of 
      Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of 
      the University of Barcelona (IBUB), Barcelona, Spain; Pediatric Research 
      Institute-Hospital Sant Joan de Deu, E-08950 Barcelona, Spain; CIBER de Diabetes 
      y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Avinguda 
      Joan XXII 27-31, E-08028 Barcelona, Spain.
FAU - Wahli, Walter
AU  - Wahli W
AD  - Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, 
      Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University 
      Singapore, 308232, Singapore; ToxAlim (Research Center in Food Toxicology), 
      INRAE, UMR1331, 31300 Toulouse Cedex, France.
FAU - Palomer, Xavier
AU  - Palomer X
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of 
      Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of 
      the University of Barcelona (IBUB), Barcelona, Spain; Pediatric Research 
      Institute-Hospital Sant Joan de Deu, E-08950 Barcelona, Spain; CIBER de Diabetes 
      y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Avinguda 
      Joan XXII 27-31, E-08028 Barcelona, Spain.
FAU - Vazquez-Carrera, Manuel
AU  - Vazquez-Carrera M
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of 
      Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of 
      the University of Barcelona (IBUB), Barcelona, Spain; Pediatric Research 
      Institute-Hospital Sant Joan de Deu, E-08950 Barcelona, Spain; CIBER de Diabetes 
      y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Avinguda 
      Joan XXII 27-31, E-08028 Barcelona, Spain. Electronic address: 
      mvazquezcarrera@ub.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230513
PL  - England
TA  - Trends Pharmacol Sci
JT  - Trends in pharmacological sciences
JID - 7906158
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - *Metformin/pharmacology/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Liver
MH  - Glucose
OTO - NOTNLM
OT  - GDF15
OT  - GLP1
OT  - hepatic glucose production
OT  - intestinal glucose uptake
OT  - metformin
OT  - microbiota
OT  - type 2 diabetes mellitus
COIS- Declaration of interests None declared by authors.
EDAT- 2023/05/16 01:09
MHDA- 2023/06/12 06:42
CRDT- 2023/05/15 21:57
PHST- 2023/03/15 00:00 [received]
PHST- 2023/04/20 00:00 [revised]
PHST- 2023/04/21 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/05/16 01:09 [pubmed]
PHST- 2023/05/15 21:57 [entrez]
AID - S0165-6147(23)00087-1 [pii]
AID - 10.1016/j.tips.2023.04.004 [doi]
PST - ppublish
SO  - Trends Pharmacol Sci. 2023 Jul;44(7):457-473. doi: 10.1016/j.tips.2023.04.004. 
      Epub 2023 May 13.