Decreased risk of liver cancer with thiazolidinediones therapy in patients with type 2 diabetes: Results from a meta-analysis

Feng, Wenquan; Zhang, Mingyue; Ma, Yanlei; Zhang, Peng; Qin, Huanlong

doi:10.1002/hep.26259

Cited by 7 publications

(5 citation statements)

References 2 publications

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“…Hence, in light of the paucity of data regarding its potential chemo-preventive role and advantage on liver-related events, along with the concern for increased cardiovascular events in patients with cirrhosis, it appears premature to recommend the preferential treatment with these drugs in patients with comorbid cirrhosis and diabetes. [31,48,[64][65][66][67][68][69][72][73][74] Again, for patients with biopsy-proven NASH, which is a common complication in patients with diabetes, the use of the TZD pioglitazone is recommended by the AASLD, given the evidence that suggests it induces regression of fibrosis in this class of patients. [75,[118][119][120][121][122][123] Unlike metformin and TZDs, sulfonylureas have consistently been reported to significantly increase the risk of HCC, especially for patients treated with secondgeneration sulfonylureas.…”

Section: Discussionmentioning

confidence: 99%

“…Wang, 2013 [72] Metanalysis including 1 RCT, 2 case control, and 2 cohort studies TZDs 900,522 patients with T2DM -NR TZDs were associated with a significantly lower risk HCC (HR = 0.73; 95% CI 0.63-0.85, p < 0.005)…”

Section: %mentioning

confidence: 99%

“…[ 67 , 68 , 70 , 71 ] With regard to the meta‐analytic evidence, in 2013 two studies reported TZD use to be associated with a significantly decreased incidence of HCC. [ 72 , 73 ] However, another metanalysis in the same year did not identify a significant protective association, although notably there was significant heterogeneity across studies. [ 31 ] More recently, a systematic review/meta‐analysis including seven studies, 280,567 participants, and 19,242 HCC cases found that TZDs use was associated with an overall reduced HCC risk (aOR 0.92, 95% CI 0.86–0.97, I 2 = 43%), which was confirmed only among Asian subjects (aOR0.90, 95% CI 0.83–0.97), but not in Western subjects (aOR 0.95, 95% CI 0.87–1.04).…”

Section: T2dm Medications and Hccmentioning

confidence: 99%

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Diabetes medications and risk of HCC

et al. 2022

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Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin‐sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: %mentioning

confidence: 99%

Section: T2dm Medications and Hccmentioning

confidence: 99%

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Diabetes medications and risk of HCC

et al. 2022

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“…SPT activity plays an important role in initiation of liver regeneration after partial hepatectomy (PHT), and its inhibition by bezafibrate negatively affects liver regeneration, presumably by decreasing the availability of plasma-borne FAs (122). The use of PPARγ agonist thiazolidinediones (pioglitazone and rosiglitazone) is associated with a decreased liver cancer incidence in T2D patients (123, 124). The association with individual sites of specific cancer differs between pioglitazone and rosiglitazone, and the underlying mechanisms require further investigation.…”

Section: Role Of Nuclear Receptors In Liver Regeneration and Hepatocementioning

confidence: 99%

Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet?

Rudraiah

Zhang

Wang

2016

Annu. Rev. Pharmacol. Toxicol.

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Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The network of target proteins associated with NRs is extremely complex, comprising coregulators, small noncoding microRNAs, and long noncoding RNAs. The importance of NRs as targets of liver disease is exemplified by the number of NR ligands that are currently used in the clinics or in clinical trials with promising results. Understanding the regulation by NR during pathophysiological conditions, and identifying ligands for orphan NR, points to a potential therapeutic approach for patients with liver diseases. An overview of complex NR metabolic networks and their pharmacological implications in liver disease is presented here.

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“…Two drugs in this class, pioglitazone and rosiglitazone, are currently available in most countries. Previous studies demonstrated that pioglitazone was associated with increased risk of bladder cancer but reduced risk of liver cancer . Moreover, a study conducted in France by Neumann et al found that pioglitazone can reduce the risk of breast cancer (hazard ratio [HR]: 0.91, 95% confidence interval [CI], 0.83‐1.00) during a median of 3.5 years' follow‐up .…”

Section: Introductionmentioning

confidence: 99%

Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta‐analysis

Lin

Cheng

et al. 2017

Diabetes Metabolism Res

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Rising experimental evidence suggests that thiazolidinediones (TZDs) exert a protective effect on breast cancer. However, studies concerning this issue were inconsistent and limited. Hence, we performed a meta-analysis with data from currently available studies to evaluate the effect of TZDs on breast cancer risk among diabetic women. We comprehensively searched for all pertinent studies addressing TZDs use and breast cancer risk published before January 1, 2016, in PubMed, Clinical Trials, and Cochrane Library. Data synthesis was performed in a random-effects model using Stata version 12.0 (Stata Corp, College Station, Texas). Fourteen independent studies were eventually selected in this meta-analysis, including 5 randomized controlled clinical trials (RCTs), 7 cohort studies, and 2 case-control studies. No significant associations of TZD use and risk of breast cancer were observed in the RCTs (pooled risk ratio [RR]: 0.77, 95% confidence interval (CI), 0.39-1.53, I = 26%) or case-control studies (pooled odds ratio, 0.99, 95% CI, 0.76-1.28, I = 31%). A 19% reduction in breast cancer risk (pooled RR: 0.81, 95% CI, 0.66-0.99, I = 72%) was found in the cohort studies. However, after removing the study with the smallest event number and the greatest effect size, the association became nonsignificant with greatly decreased heterogeneity (pooled RR: 0.94, 95% CI, 0.86-1.03, I = 16%). This meta-analysis did not find any significant association between TZDs use and risk of breast cancer among diabetic women.

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Decreased risk of liver cancer with thiazolidinediones therapy in patients with type 2 diabetes: Results from a meta-analysis

Cited by 7 publications

References 2 publications

Diabetes medications and risk of HCC

Diabetes medications and risk of HCC

Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet?

Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta‐analysis

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