Thiazolidinediones versus metformin on improving abnormal liver enzymes in patients with type 2 diabetes mellitus: a meta-analysis

Chunmei Xu _, Junyu Zhao, Xiaojun Zhou, Rui Zhang, Tianyue Xie, Zhiwei Zou, Lin Liao and Jianjun Dong

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Oncotarget. 2018; 9:12389-12399. https://doi.org/10.18632/oncotarget.24222

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Chunmei Xu1,*, Junyu Zhao1,*, Xiaojun Zhou1, Rui Zhang1, Tianyue Xie3, Zhiwei Zou2, Lin Liao1 and Jianjun Dong2

1Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China

2Department of Medicine, Division of Endocrinology, Qilu Hospital of Shandong University, Shandong University, Jinan, China

3Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, China

*Co-first authors and equal contribution to this work

Correspondence to:

Lin Liao, email: [email protected]

Jianjun Dong, email: [email protected]

Keywords: liver enzyme abnormalities; thiazolidinediones; metformin; randomized controlled trials; meta-analysis

Received: August 01, 2017     Accepted: December 05, 2017     Published: January 13, 2018


Background: Liver enzyme abnormalities are common in patients with type 2 diabetes. Currently, the inverse relationship between elevated liver enzymes and antidiabetics intake may be explained by rigorous treatment and good control. However, few studies have directly explored the influence of antidiabetics on abnormal liver function, especially the comparison between two insulin sensitizers—thiazolidinediones and metformin.

Materials And Methods: Databases, including PubMed, Cochrane, CNKI, Wanfang and VIP were searched. Two reviewers performed independently. Meta-analysis was used when studies were homogeneous enough.

Results: Six studies, including 4726 patients with type 2 diabetes, were involved in this systematic review. Compared with metformin, thiazolidinediones significantly reduced the alanine transaminase, aspartate aminotransferase and gamma-glutamyl transpeptidase. Further subgroup analysis suggested that pioglitazone-treated participants showed vast improvement in decreasing alanine transaminase (MD = -13.70; 95% CI = -16.91 to -10.52; P < 0.00001; I² = 1%), aspartate aminotransferase (MD = -3.51; 95% CI = -5.74 to –1.28; P = 0.002; I² = 0%) and gamma-glutamyl transpeptidase (MD = -5.41; 95% CI = -9.40 to -1.42; P = 0.008; I² = 0%), while rosiglitazone exhibited no difference in lowering corresponding liver enzyme levels. Besides, thiazolidinediones similarly decreased fasting plasma glucose. However, thiazolidinediones were inferior to metformin in lowering HbA1C and alkaline phosphatase. Additionally, no significant publication bias was seen.

Conclusions: Thiazolidinediones may confer modest biological improvement of liver function in people with type 2 diabetes than metformin. But owing to the limited methodological quality, more clinical researches are warranted in the future.

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