Systematic Review with Network Meta-Analysis: Antidiabetic Medication and Risk of Hepatocellular Carcinoma

Yao-Yao Zhou, Gui-Qi Zhu, Tian Liu, Ji-Na Zheng, Zhang Cheng, Tian-Tian Zou, Martin Braddock, Shen-Wen Fu, Ming-Hua Zheng, Yao-Yao Zhou, Gui-Qi Zhu, Tian Liu, Ji-Na Zheng, Zhang Cheng, Tian-Tian Zou, Martin Braddock, Shen-Wen Fu, Ming-Hua Zheng

Abstract

Antidiabetic medication may modify the incidence of hepatocellular carcinoma (HCC). We aimed to compare the use of different antidiabetic strategies and the incidence of HCC. PubMed, Embase.com and Cochrane Library databases were searched up to 31 October 2015 and randomized controlled trials (RCTs), cohort studies or case-control studies were included for our analyses. A total of thirteen studies enrolling 481358 participants with 240678 HCC cases who received at least two different strategies were retrieved in this analysis. Direct comparisons showed that use of metformin (risk ratio [RR] 0.49, 95% CI 0.25-0.97) was associated with a significant risk reduction of HCC, while insulin (RR = 2.44, 95% CI 1.10- 5.56) may significantly increase the risk. Indirect evidence also suggested that insulin (RR = 2.37, 95% CI 1.21-4.75) was associated with a significantly increased risk of HCC. Additionally, metformin was effective in reducing the risk of HCC when compared with sulphonylurea (RR = 0.45, 95% CI 0.27-0.74) and insulin (RR = 0.28, 95% CI 0.17-0.47). Notably, metformin was hierarchically the best when compared with other antidiabetic therapies for the prevention of HCC. In summary, available evidence suggests that metformin was the most effective strategy to reduce HCC risk when compared with other antidiabetic interventions.

Figures

Figure 1. Literature search and selection.
Figure 1. Literature search and selection.
Figure 2. Network of the comparisons for…
Figure 2. Network of the comparisons for the Bayesian network meta-analysis.
The size of every node is proportional to the number of patients. The width of the lines is proportional to the number of trials or pairs of trial arms.
Figure 3. Pooled odds ratios for HCC…
Figure 3. Pooled odds ratios for HCC incidence.
The column treatment is compared with the row treatment. Numbers in parentheses indicate 95% confidence intervals.
Figure 4. Rankograms showing probability of each…
Figure 4. Rankograms showing probability of each strategy have each rank (1–5) for HCC incidence.
Ranking indicates the probability to be the best treatment, the second best, the third best and so on. Specifically, rank 1 is worst and rank N is best.
Figure 5. Comparison-adjusted funnel plot.
Figure 5. Comparison-adjusted funnel plot.
The red dotted line represents the null hypothesis that the study-specific effect sizes cannot differ from the respective comparison-specific pooled effect estimates. The two black dashed lines represent a 95% CI for the difference between study-specific effect sizes and comparison-specific summary estimates. Different colors correspond to different comparisons. Yixy is the noted effect size in study i that compares x with y. μxy is the comparison-specific summary estimate for x versus y.

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