PMID- 27987248
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20220408
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 19
IP  - 4
DP  - 2017 Apr
TI  - Understanding and overcoming metformin gastrointestinal intolerance.
PG  - 473-481
LID - 10.1111/dom.12854 [doi]
AB  - Metformin is the most widely prescribed drug for patients with type 2 diabetes 
      mellitus and the first-line pharmacological option as supported by multiple 
      international guidelines, yet a rather large proportion of patients cannot 
      tolerate metformin in adequate amounts because of its associated gastrointestinal 
      (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy 
      include diarrhoea, nausea, flatulence, indigestion, vomiting and abdominal 
      discomfort, with diarrhoea and nausea being the most common. Although starting at 
      a low dose and titrating slowly may help prevent some GI AEs associated with 
      metformin, some patients are unable to tolerate metformin at all and it may also 
      be difficult to convince patients to start metformin again after a bout of GI 
      AEs. Despite this clinical importance, the underlying mechanisms of the GI 
      intolerance associated with metformin are poorly known. In the present review, we 
      discuss: the epidemiology of metformin-associated GI intolerance and its 
      underlying mechanisms; genotype variability and associated factors affecting 
      metformin GI intolerance, such as comorbidities, co-medications and bariatric 
      surgery; clinical consequences and therapeutic strategies to overcome metformin 
      GI intolerance. These strategies include appropriate titration of 
      immediate-release metformin, use of extended-release metformin, the promise of 
      delayed-release metformin and gut microbiome modulators, as well as alternative 
      pharmacological therapies when metformin cannot be tolerated at all. Given the 
      available data, all efforts should be made to maintain metformin before 
      considering a shift to another drug therapy.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Bonnet, Fabrice
AU  - Bonnet F
AD  - Department of Endocrinology, Diabetes and Nutrition, Centre Hospitalier 
      Universitaire de Rennes, Rennes, France.
FAU - Scheen, Andre
AU  - Scheen A
AUID- ORCID: 0000-0001-9743-4371
AD  - Department of Endocrinology, Diabetes and Nutrition, Division of Clinical 
      Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), 
      University of Liege, CHU, Liege, Belgium.
AD  - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, 
      University of Liege CHU, Liege, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170222
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Gastrointestinal Diseases/*chemically induced
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - Metformin/*adverse effects
OTO - NOTNLM
OT  - gastrointestinal intolerance
OT  - metformin
OT  - microbiota
OT  - type 2 diabetes mellitus
EDAT- 2016/12/18 06:00
MHDA- 2017/11/03 06:00
CRDT- 2016/12/18 06:00
PHST- 2016/09/26 00:00 [received]
PHST- 2016/12/11 00:00 [revised]
PHST- 2016/12/12 00:00 [accepted]
PHST- 2016/12/18 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2016/12/18 06:00 [entrez]
AID - 10.1111/dom.12854 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2017 Apr;19(4):473-481. doi: 10.1111/dom.12854. Epub 2017 
      Feb 22.