Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials
Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials
Aim
There are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease.
Methods
We systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH.
Results
We included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n = 6 studies), glitazones (n = 8 studies), glucagon-like peptide-1 receptor agonists (n = 6 studies), dipeptidyl peptidase-4 inhibitors (n = 4 studies) or sodium-glucose cotransporter-2 inhibitors (n = 7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only.
Conclusion
RCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD.
Anti-hyperglycaemic drugs, NAFLD, NASH, Type 2 diabetes
427-441
Mantovani, Alessandro
19fc8a1f-60fe-403a-b70e-6b6884929e03
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Scorletti, Eleonora
4e896544-2974-4f81-9696-1595d3c36814
Scorletti, Eleonora
42bb0659-ac67-4a73-bf36-a881fe6c1563
Mantzoros, Christos S.
e079c112-0163-481c-aea6-1c3d0f68c2a4
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
1 November 2020
Mantovani, Alessandro
19fc8a1f-60fe-403a-b70e-6b6884929e03
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Scorletti, Eleonora
4e896544-2974-4f81-9696-1595d3c36814
Scorletti, Eleonora
42bb0659-ac67-4a73-bf36-a881fe6c1563
Mantzoros, Christos S.
e079c112-0163-481c-aea6-1c3d0f68c2a4
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Mantovani, Alessandro, Byrne, Christopher, Scorletti, Eleonora, Scorletti, Eleonora, Mantzoros, Christos S. and Targher, Giovanni
(2020)
Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials.
Diabetes & Metabolism, 46 (6), .
(doi:10.1016/j.diabet.2019.12.007).
Abstract
Aim
There are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease.
Methods
We systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH.
Results
We included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n = 6 studies), glitazones (n = 8 studies), glucagon-like peptide-1 receptor agonists (n = 6 studies), dipeptidyl peptidase-4 inhibitors (n = 4 studies) or sodium-glucose cotransporter-2 inhibitors (n = 7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only.
Conclusion
RCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD.
Text
Glucose-lowering drugs for NAFLD_Systematic review R1 version
- Accepted Manuscript
Text
Supplementary Figure S1 PRISMA Flow Chart
- Accepted Manuscript
Text
Supplementary Table S1 R1 version
- Accepted Manuscript
More information
Accepted/In Press date: 27 December 2019
e-pub ahead of print date: 7 January 2020
Published date: 1 November 2020
Keywords:
Anti-hyperglycaemic drugs, NAFLD, NASH, Type 2 diabetes
Identifiers
Local EPrints ID: 436859
URI: http://eprints.soton.ac.uk/id/eprint/436859
ISSN: 1262-3636
PURE UUID: ecf57a85-f3de-48fa-ad95-16e001182ca7
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Date deposited: 13 Jan 2020 17:30
Last modified: 17 Mar 2024 05:11
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Contributors
Author:
Alessandro Mantovani
Author:
Eleonora Scorletti
Author:
Eleonora Scorletti
Author:
Christos S. Mantzoros
Author:
Giovanni Targher
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