Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes

Han, Eugene; Jang, Suk‐Yong; Kim, Gyuri; Lee, Yong-Ho; Choe, Eun Yeong; Nam, Chung Mo; Kang, Eun Seok

doi:10.1097/md.0000000000002786

Cited by 30 publications

(29 citation statements)

References 34 publications

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“…Previous cancer was defined as the presence of other different primary cancers that were diagnosed prior to HCC diagnosis, except for liver cancers (intrahepatic bile duct carcinoma, hepatoblastoma, angiosarcoma, and other sarcomas), pancreatic or biliary tract cancers (gallbladder, biliary tract, and pancreatic cancer), and any cancers most likely to metastasize to the liver (stomach, colon, bronchus and lung, and breast) . We also adjusted for the Charlson comorbidity score, antidiabetic medications (insulin, sulfonylurea, metformin and thiazolidinedione), aspirin use, household income and residential area . As there was incomplete information regarding the smoking and alcohol drinking habits of individuals in the NHIS‐NSC, we assumed that chronic lower respiratory disease and alcoholic liver disease as well as alcohol‐related mental and behavioral disorders could be used as surrogate variables for cigarette smokers and alcohol use, respectively.…”

Section: Methodsmentioning

confidence: 99%

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Kim

Jang

Han

et al. 2016

Intl Journal of Cancer

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Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5-year HCC-free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22-0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14-0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32-1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose-dependent manner, especially in individuals with liver disease.

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Section: Methodsmentioning

confidence: 99%

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Kim

Jang

Han

et al. 2016

Intl Journal of Cancer

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“…Traditionally, thiazolidinediones (TZDs) are the first-line treatment for patients with comorbid T2D and NAFLD [4]. TZDs are peroxisome proliferator-activated receptor gamma agonists that improve glucose tolerance and insulin sensitivity and enhance insulin action in the muscle, liver, and heart as well as in adipose tissue [5][6][7]. TZDs in patients with comorbid T2D and NAFLD have been shown to improve liver enzymes and hepatic histology [8].…”

Section: Introductionmentioning

confidence: 99%

Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial

Han

Lee

et al. 2020

JCM

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Despite the benefits of pioglitazone in the treatment of non-alcoholic fatty liver disease (NAFLD), many treated patients continue to experience disease progression. We aimed to investigate the additive effect of ipragliflozin on NAFLD in patients with type 2 diabetes treated with metformin and pioglitazone. In this 24-week randomized controlled trial, 44 patients with type 2 diabetes and comorbid NAFLD were either randomized to receive 50 mg/day of ipragliflozin as an add-on treatment (n = 29) or maintained on metformin and pioglitazone (n = 15). The fatty burden was assessed using the fatty liver index, NAFLD liver fat score, and controlled attenuation parameter (CAP). Changes in fat and muscle depots were measured by dual-energy x-ray absorptiometry and abdominal computed tomography scans. The enrolled patients were relatively controlled (mean baseline glycated hemoglobin of 6.6% ± 0.6%) and centrally obese (mean waist circumference of 101.6 ± 10.9 cm). At week 24, patients in the ipragliflozin add-on group exhibited reduced hepatic fat content (fatty liver index: −9.8 ± 1.9, p = 0.002; NAFLD liver fat score: −0.5 ± 0.2, p = 0.049; CAP: −8.2 ± 7.8 dB/m2, p = 0.133). Ipragliflozin add-on therapy also reduced whole-body visceral fat and the ratio of visceral to subcutaneous fat (change in whole-body visceral fat: −69.6 ± 21.5 g; change in abdominal visceral fat: −26.2 ± 3.7 cm2; abdominal visceral to subcutaneous fat ratio: −0.15 ± 0.04; all p < 0.05). In conclusion, ipragliflozin treatment significantly ameliorates liver steatosis and reduces excessive fat in euglycemic patients with type 2 diabetes and NAFLD taking metformin and pioglitazone.

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“…Twenty studies (12 cohort studies and eight case-control studies) involving 4,846,088 individuals reported adjusted estimates of bladder cancer [6,[8][9][10][11][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] (Table S2). Two studies used the same research database (UK General Practice Research Database) [31,39], which might lead to overlapping patients.…”

Section: Evidence Of Observational Studiesmentioning

confidence: 99%

Pioglitazone and bladder cancer risk: a systematic review and meta‐analysis

et al. 2018

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Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta‐analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least‐squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever‐users of pioglitazone versus never‐users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time‐ (P = 0.003) and dose‐dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner. Patients with long‐term and high‐dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

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Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes

Abstract: Supplemental Digital Content is available in the text

Cited by 30 publications

References 34 publications

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial

Pioglitazone and bladder cancer risk: a systematic review and meta‐analysis

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