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

• Published in: Diabetes & metabolism Vol. 46; no. 6; pp. 427 - 441
• Main Authors: Mantovani, A., Byrne, C.D., Scorletti, E., Mantzoros, C.S., Targher, G.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-11-2020
• Subjects: Anti-hyperglycaemic drugs; NAFLD; NASH; Type 2 diabetes; Type 2 diabetes; NAFLD; Anti-hyperglycaemic drugs; NASH
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2019.12.007

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.
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.
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.
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.