Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study

Lin, Herng Ching; Hsu, Yung‐Ho; Kachingwe, Baxter Hepburn; Hsu, Chung-Yi; Uang, Yow Shieng; Wang, L. H.

doi:10.1111/jcpt.12151

Cited by 36 publications

(36 citation statements)

References 45 publications

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“…In particular, in agreement with other studies (Bosetti et al, 2013;Singh et al, 2013;Lin et al, 2014), no association was evident with pancreatic cancer. Chang et al (2012), however, suggest that different thiazolidinediones might have different effects on cancer occurrence.…”

Section: Accepted Manuscriptsupporting

confidence: 93%

Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study

Valent¹

2015

Journal of Diabetes and its Complications

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Section: Accepted Manuscriptsupporting

confidence: 93%

Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study

Valent¹

2015

Journal of Diabetes and its Complications

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“…We acquired 5,318 reports. After title and abstract screening, 178 were potentially eligible (including 159 potentially relevant RCTs and 19 potentially relevant observational studies19202122232425262728293031323334353637). Ultimately, 14 RCTs1314151617183839404142434445 involving 2881 patients, proved eligible, and no observational studies were included.…”

Section: Resultsmentioning

confidence: 99%

Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

Zhang

Chen

et al. 2016

Sci Rep

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Alpha-glucosidase inhibitors (AGIs) was reported to be associated with several rare adverse hepatic events, but with inconsistent results. We aimed to investigate the risk of hepatotoxicity associated with the use of AGIs in patients with type 2 diabetes mellitus (T2DM), and performed a systematic review and meta-analysis. Fourteen studies (n = 2881) were eligible, all of which were RCTs. Meta-analysis of data regarding elevation of more than 3-fold the upper limit of normal (ULN) of AST and ALT showed statistically significant differences between AGIs treatment versus control (OR 6.86, 95% CI 2.50 to 18.80; OR 6.48, 95% CI 2.40 to 17.49). Subgroup analyses of elevation of more than 1.8-fold ULN of AST and ALT by dose of AGIs showed differential effects on AST and ALT (AST: OR 0.38 vs 7.31, interaction P = 0.003; ALT: OR 0.32 vs 4.55, interaction p = 0.02). Meta-analysis showed that AGIs might increase the risk of hepatotoxicity, and higher dose appeared to be associated with higher risk of hepatotoxicity. However, the evidence is limited with surrogate measures (i.e. ALT and AST), and no clinically important adverse events were observed.Alpha-glucosidase inhibitors (AGIs) are commonly used oral hypoglycemic drugs, especially in the patient population from East Asia 1-3 . The guideline of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommended the use of AGIs as a potentially first-line agent or in combination with other antihyperglycemic drugs 4 . AGIs has proven similarly efficacious as other commonly used antidiabetes agents [5][6][7] . A recent large trial 1 showed that acarbose is similar to metformin in terms of efficacy, and supports a viable choice for initial therapy in patients with newly diagnosed type 2 diabetes. Additionally, AGIs do not increase body weight, rarely cause hypoglycemia; and have minimal drug-drug interactions 1,7,8 . Meanwhile, AGIs was reported to be associated with several rare adverse hepatic events 9-11 and increase liver enzyme levels [12][13][14][15][16][17][18] . The causal relationship, however, has not been established 9 , and the magnitude of effect on the increase of liver enzyme levels remains unclear. Because these issues are often treated as adverse effects issues, and the hepatic adverse events, if any, are usually rare, individual trials are not adequate to address these important clinical questions. A meta-analysis -in which multiple studies are pooled -may offer opportunity to detect a small but clinically important difference.Thus, we carried out a systematic review of randomized controlled trials and observational studies to assess the association between hepatotoxicity and AGIs. We hypothesized that hepatotoxicity would be more frequently manifested in AGIs as opposed to no use. Figure 1 showed the study selection process. We acquired 5,318 reports. After title and abstract screening, 178 were potentially eligible (including 159 potentially relevant RCTs and 19 potentially relevant observational studies [1...

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“…A systematic review and meta-analysis of 840, 787 diabetic patients did not support an association between thiazolidinediones and CRC [229, 230]. In a 6-year population-based cohort study, thiazolidinediones were associated with decreased cancer risk including CRC and the association was dose-dependent [231]. Thiazolidinediones have cytostatic effects and inhibit growth and metastasis of colon cancer cells as they induce differentiation and modulate the E-cadherin/β-catenin system [232–234].…”

Section: Implications For Therapymentioning

confidence: 99%

2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

et al. 2017

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Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer.

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Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study

Abstract: The results showed a decrease in cancer risk in diabetic patients using TZD, and the association was dose dependent.

Cited by 36 publications

References 45 publications

Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study

Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study

Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

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