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

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

SUBMITTER: Xu C

PROVIDER: S-EPMC5844755 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Xu Chunmei C Zhao Junyu J Zhou Xiaojun X Zhang Rui R Xie Tianyue T Zou Zhiwei Z Liao Lin L Dong Jianjun J

Oncotarget 20180113 15

<h4>Background</h4>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.<h4>Materials and methods</h4>Databases, including PubMed, Cochran ...[more]

PMID: 29552319

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Project description:Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet β-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet β-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.

Project description:BackgroundMultiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS.MethodsWe identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed.ResultsTwenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events.ConclusionsOurs is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524.

Project description:ImportanceNonalcoholic steatohepatitis (NASH) is projected to be the leading cause of liver transplantation by 2020. Advanced fibrosis (stage F3-F4) on liver biopsy independently predicts all-cause and liver-related mortality in NASH. There are no known efficacious treatments for advanced fibrosis related to NASH. Thiazolidinedione therapy has been extensively evaluated in NASH, and new randomized clinical trials (RCTs) of its efficacy have been completed.ObjectiveTo synthesize the evidence about the association of thiazolidinedione therapy with advanced liver fibrosis in NASH.Data sourcesMEDLINE, Ovid MEDLINE In-Process, Cochrane Library, EMBASE, clinicaltrials.gov, PubMed, and Scopus databases (without language restrictions), as well as other registries and scientific meeting presentations, from database inception through August 15, 2016.Study selectionRandomized clinical trials evaluating the effect of thiazolidinedione therapy on histologic features of the liver in biopsy-proven NASH.Data extraction and synthesisTwo investigators extracted study data independently and in duplicate and rated the risk of bias using the Cochrane Risk of Bias Tool.Main outcomes and measuresThe primary outcome was a dichotomous improvement in advanced fibrosis on liver biopsy, defined as an improvement in fibrosis stage from F3-F4 to F0-F2. Secondary outcomes were at least a 1-point improvement in fibrosis of any stage and NASH resolution. This meta-analysis also evaluated adverse effects of thiazolidinedione therapy, including weight gain, lower limb edema, congestive heart failure, bone fractures, cancer, and anemia. With the use of random-effects models, dichotomous variables are presented as odds ratios (ORs) with 95% CIs, and continuous variables are presented as weighted mean differences with 95% CIs.ResultsThis study analyzed 8 RCTs (5 evaluating pioglitazone use and 3 evaluating rosiglitazone maleate use) enrolling 516 patients with biopsy-proven NASH for a duration of 6 to 24 months. Among all studies combined, thiazolidinedione therapy was associated with improved advanced fibrosis (OR, 3.15; 95% CI, 1.25-7.93; P = .01; I2 = 0%), fibrosis of any stage (OR, 1.66; 95% CI, 1.12-2.47; P = .01; I2 = 0%), and NASH resolution (OR, 3.22; 95% CI, 2.17-4.79; P < .001; I2 = 0%). Analyses restricted to RCTs enrolling patients without diabetes yielded similar results for improvement in advanced fibrosis (OR, 2.95; 95% CI, 1.04-10.90; P = .02; I2 = 0%), improvement in fibrosis of any stage (OR, 1.76; 95% CI, 1.02-3.03; P = .02; I2 = 0%), and NASH resolution (OR, 3.40; 95% CI, 1.95-5.93; P < .001; I2 = 0%). All effects were accounted for by pioglitazone use. Weight gain and lower limb edema occurred more frequently with thiazolidinedione therapy (initial body weight +2.70%; 95% CI, 1.96%-4.34%; P = .001). The small sample size of included RCTs prevented evaluation of more serious adverse effects of thiazolidinedione therapy.Conclusions and relevancePioglitazone use improves advanced fibrosis in NASH, even in patients without diabetes. Whether this finding translates to improvement in risk for clinical outcomes requires further study.

Project description:The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = - 0.09, 95% CI - 0.2, 0.02; p = 0.092) or those without metformin therapy (β = - 0.05, 95% CI - 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient's condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation.

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

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

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