Risk of bladder cancer in patients with diabetes: a retrospective cohort study

ObjectiveTo investigate trends in incident and prevalent diagnoses of type 2 diabetes mellitus (T2DM) and its pharmacological treatment between 2000 and 2013.DesignAnalysis of longitudinal electronic health records in The Health Improvement Network (THIN) primary care database.SettingUK primary care.ParticipantsIn total, we examined 8 838 031 individuals aged 0–99 years.Outcome measuresThe incidence and prevalence of T2DM between 2000 and 2013, and the effect of age, sex and social deprivation on these measures were examined. Changes in prescribing patterns of antidiabetic therapy between 2000 and 2013 were also investigated.ResultsOverall, 406 344 individuals had a diagnosis of T2DM, of which 203 639 were newly diagnosed between 2000 and 2013. The incidence of T2DM rose from 3.69 per 1000 person-years at risk (PYAR) (95% CI 3.58 to 3.81) in 2000 to 3.99 per 1000 PYAR (95% CI 3.90 to 4.08) in 2013 among men; and from 3.06 per 1000 PYAR (95% CI 2.95 to 3.17) to 3.73 per 1000 PYAR (95% CI 3.65 to 3.82) among women. Prevalence of T2DM more than doubled from 2.39% (95% CI 2.37 to 2.41) in 2000 to 5.32% (95% CI 5.30 to 5.34) in 2013. Being male, older, and from a more socially deprived area was strongly associated with having T2DM, (p<0.001). Prescribing changes over time reflected emerging clinical guidance and novel treatments. In 2013, metformin prescribing peaked at 83.6% (95% CI 83.4% to 83.8%), while sulfonylureas prescribing reached a low of 41.4% (95% CI 41.1% to 41.7%). Both remained, however, the most commonly used pharmacological treatments as first-line agents and add-on therapy. Thiazolidinediones and incretin based therapies (gliptins and GLP-1 analogues) were also prescribed as alternate add-on therapy options, however were rarely used for first-line treatment in T2DM.ConclusionsPrevalent cases of T2DM more than doubled between 2000 and 2013, while the number of incident cases increased more steadily. Changes in prescribing patterns observed may reflect the impact of national policies and prescribing guidelines on UK primary care.

show abstract

“…2 Hence, primary care data from the UK is increasingly being used to study the disease and its management. 3 4 …”

Section: Introductionmentioning

confidence: 99%

Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study

2016

View full text Add to dashboard Cite

show abstract

“…In the 2014 National Diabetes Statistics Report, the Centers for Disease Control and Prevention estimated that 29.1 million people (9.3% of the population) are diagnosed with diabetes in the United States [9]. Worldwide, an estimated 382 million adults were diagnosed with diabetes in 2013 [10], with type II diabetes accounting for nearly 90–95% of these diabetic individuals [11]. …”

Section: Introductionmentioning

confidence: 99%

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

et al. 2017

View full text Add to dashboard Cite

The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.

show abstract

“…We noticed a non‐significantly increased risk of UBC (HR = 1.14, 95% CI 0.88, 1.48) during the first year after the first ADD prescription, compared with controls. A same increase in risk has been seen after diabetes diagnosis most likely indicating the presence of detection bias. The sensitivity analyses inducing a time lag period of 180, 360 or 720 days did not confirm the hypothesis that the increased risk detected during the first year was due to metformin (HR = 1.11, 95% CI 0.84, 1.47 for 360 days time lag period).…”

Section: Discussionmentioning

confidence: 61%

“…Although this cohort still contained 12 841 women with diagnosis of polycystic ovarian syndrome (PCOS), rare off‐label indications are unlikely affect pharmacological hypothesis. A sensitivity‐analysis excluding these PCOS patients estimating the risk of bladder cancer in diabetes patients compared with non‐diabetes controls did not alter the results in the same cohort of diabetic patients . We preferred to use an inception cohort instead of a nested case–control design.…”

Section: Discussionmentioning

confidence: 99%

“…In 2012, more than 400 000 bladder cancer (UBC) cases occurred worldwide, making it the seventh most common type of cancer . Although most cohort and case–control studies demonstrated an increased risk of UBC due to type 2 diabetes compared with non‐diabetic controls with a relative risk (RR) ranging from 1.11 (95% CI 1.00, 1.23) to 1.32 (95% CI 1.18, 1.49) adjusted for smokers , neither the risk of UBC nor the mortality from UBC was increased in patients with type 1 and patients with type 2 diabetes in the UK Clinical Practice Research Datalink (CPRD) with a hazard ratio (HR) of 0.77 (95% CI 0.57, 1.05) and 1.04 (95% CI 0.96, 1.14) for type 1 and 2 diabetes, respectively . The influence of different anti‐diabetic drugs (ADD), especially metformin, on the risk of UBC is still unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients

Goossens

Buntinx

Driessen

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aim The aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort). Methods We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti‐diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP‐4‐inhibitors, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration. Results The inception cohort included 165 398 participants of whom 132 960 were metformin users and 32 438 were SU only users. During a mean follow‐up time of more than 5 years 693 patients developed UBC, 124 of the control group and 461 of the all metformin users. There was no association between metformin use and UBC risk (HR = 1.12, 95% CI 0.90, 1.40) compared with SU only users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant. Conclusion Metformin has no influence on the risk of UBC compared with SU in type 2 diabetes patients using a new user design.

show abstract

Risk of bladder cancer in patients with diabetes: a retrospective cohort study

Cited by 19 publications

References 31 publications

Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study

Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients

Contact Info

Product

Resources

About