PMID- 37938366
OWN - NLM
STAT- MEDLINE
DCOM- 20240111
LR  - 20240113
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 80
IP  - 1
DP  - 2024 Jan
TI  - The role of anti-diabetic drugs in NAFLD. Have we found the Holy Grail? A 
      narrative review.
PG  - 127-150
LID - 10.1007/s00228-023-03586-1 [doi]
AB  - PURPOSE: Non-alcoholic fatty liver disease (NAFLD) has become a leading cause of 
      liver disease, affecting 30% of the global population. NAFLD prevalence is 
      particularly high in obese individuals and patients with type 2 diabetes mellitus 
      (T2DM). NAFLD ranges from simple fat deposition in the liver to necroinflammation 
      and fibrosis (non-alcoholic steatohepatitis (NASH)), NASH-cirrhosis, and/or 
      hepatocellular carcinoma. Insulin resistance plays a key role in NAFLD 
      pathogenesis, alongside dysregulation of adipocytes, mitochondrial dysfunction, 
      genetic factors, and changes in gut microbiota. Since insulin resistance is also 
      a major predisposing factor of T2DM, the administration of anti-diabetic drugs 
      for the management of NAFLD seems reasonable. METHODS: In this review we provide 
      the NAFLD-associated mechanisms of action of some of the most widely used 
      anti-diabetic drugs, namely metformin, pioglitazone, sodium-glucose transport 
      protein-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor analogs (GLP1 
      RAs), and dipeptyl-peptidase-4 inhibitors (DPP4i) and present available data 
      regarding their use in patients with NAFLD, with and without T2DM. RESULTS: Both 
      metformin and DPP4i have shown rather contradictory results, while pioglitazone 
      seems to benefit patients with NASH and is thus the only drug approved for NASH 
      with concomitant significant liver fibrosis by all major liver societies. On the 
      other hand, SGLT2i and GLP1 RAs seem to be beneficiary in patients with NAFLD, 
      showing both remarkable results, with SGLT2i proving to be more efficient in the 
      only head-to-head study so far. CONCLUSION: In patients with NAFLD and diabetes, 
      pioglitazone, GLP1 RAs, and SGLT2i seem to be logical treatment options. Larger 
      studies are needed before these drugs can be recommended for non-diabetic 
      individuals.
CI  - (c) 2023. The Author(s).
FAU - Zachou, Maria
AU  - Zachou M
AUID- ORCID: 0000-0001-5156-9553
AD  - Gastroenterology Department, "Sismanoglio" General Hospital, 151 26, Athens, 
      Greece.
FAU - Flevari, Pagona
AU  - Flevari P
AUID- ORCID: 0000-0001-8638-7944
AD  - Expertise Center in Rare Haematological Diseases-Haemoglobinopathies, "Laiko" 
      General Hospital, 115 27, Athens, Greece.
FAU - Nasiri-Ansari, Narjes
AU  - Nasiri-Ansari N
AUID- ORCID: 0000-0002-0116-693X
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 115 27, Athens, Greece.
FAU - Varytimiadis, Constantinos
AU  - Varytimiadis C
AUID- ORCID: 0000-0002-6155-685X
AD  - Gastroenterology Department, "Evangelismos" General Hospital, 106 76, Athens, 
      Greece.
FAU - Kalaitzakis, Evangelos
AU  - Kalaitzakis E
AUID- ORCID: 0000-0002-9947-8914
AD  - Department of Gastroenterology, University Hospital of Heraklion, University of 
      Crete, 715 00, Heraklion, Greece.
FAU - Kassi, Eva
AU  - Kassi E
AUID- ORCID: 0000-0001-7491-2297
AD  - Unit of Molecular Endocrinology, Department of Biological Chemistry, Medical 
      School, National and Kapodistrian University of Athens, 115 27, Athens, Greece.
AD  - Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, "Laiko" 
      Hospital, National and Kapodistrian University of Athens, 115 27, Athens, Greece.
FAU - Androutsakos, Theodoros
AU  - Androutsakos T
AUID- ORCID: 0000-0003-2556-6230
AD  - Department of Pathophysiology, Medical School, National and Kapodistrian 
      University of Athens, Mikras Asias 75, 115 27, Athens, Greece. 
      tandroutsak@med.uoa.gr.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20231108
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - X4OV71U42S (Pioglitazone)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Humans
MH  - *Non-alcoholic Fatty Liver Disease/drug therapy/epidemiology/pathology
MH  - Pioglitazone/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy/complications
MH  - Hypoglycemic Agents/adverse effects
MH  - *Insulin Resistance/physiology
MH  - *Metformin/pharmacology
MH  - Liver Cirrhosis/drug therapy/complications
PMC - PMC10781828
OTO - NOTNLM
OT  - Glucagon-like peptide-1
OT  - Metabolic associated fatty liver disease
OT  - Metformin
OT  - Non-alcoholic fatty liver disease
OT  - Pioglitazone
OT  - Sodium-glucose transporter inhibitors
COIS- The authors declare no competing interests.
EDAT- 2023/11/08 12:42
MHDA- 2024/01/11 07:43
PMCR- 2023/11/08
CRDT- 2023/11/08 11:19
PHST- 2023/07/01 00:00 [received]
PHST- 2023/10/19 00:00 [accepted]
PHST- 2024/01/11 07:43 [medline]
PHST- 2023/11/08 12:42 [pubmed]
PHST- 2023/11/08 11:19 [entrez]
PHST- 2023/11/08 00:00 [pmc-release]
AID - 10.1007/s00228-023-03586-1 [pii]
AID - 3586 [pii]
AID - 10.1007/s00228-023-03586-1 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2024 Jan;80(1):127-150. doi: 10.1007/s00228-023-03586-1. 
      Epub 2023 Nov 8.