What is Pioglitazone?
Pioglitazone belongs to a group of medicines known as thiazolidinediones (or Glitazones)
used for the management of Type 2 diabetes in addition to diet and exercise.1
Pioglitazone works by increasing the body’s sensitivity to insulin, a natural substance
produced by the pancreas that helps control blood glucose levels. Pioglitazone’s action
that increases the body’s sensitivity to insulin is linked to its ability to bind to peroxisome
proliferator-activated receptor-gamma (PPARγ) receptors found in tissues such as
adipose tissue, skeletal muscle, and liver. Activation of PPARγ receptors is important for
insulin’s glucose-lowering action in the body.
Pioglitazone is not used to treat Type 1 diabetes (a condition in which the body does not
produce insulin) or diabetic ketoacidosis (a serious condition that may develop in Type 1
and sometimes Type 2 diabetes if high blood glucose is not treated). In addition to the
use of Pioglitazone to control blood glucose in Type 2 diabetes, there is evidence that it
could reduce the number of heart attacks in people living with diabetes.2 On the other
hand, there have also been concerns that the use of Pioglitazone may be associated with
the risk of developing cancer of the urinary bladder. However, while some studies suggest
that this may be the case, others suggest no added risk
What is Bladder cancer?
Bladder cancer is cancer that starts in the urinary bladder. The urinary bladder is a
hollow, muscular organ in the lower abdomen
The bladder’s role is to hold urine until it leaves the body through the urethra.
Bladder cancer begins when cells in the urinary bladder start to grow uncontrollably. As
more cancer cells develop, they can spread to other areas of the body
What is the Evidence that Pioglitazone causes Bladder Cancer?
The findings of a five year interim analysis of a large observational study using the Kaiser
Permanente Northern California database showed that the use of pioglitazone for 24
months or more was associated with an increased risk of bladder cancer.4 However, in
the final analysis of the Kaiser Permanente Northern California study, which used the
same cohort with follow-up extended to ten years, the use of pioglitazone was no longer
significantly associated with an increased risk of bladder cancer in a duration-response
fashion.5 The most recent meta-analysis which reviewed twenty-six studies found no
difference in the incidence of bladder cancer among patients using pioglitazone compared
with non-users.
How could Pioglitazone increase the risk of Bladder Cancer?
Although studies suggest PPARγ agonists are involved in known tumour-suppression
pathways, mechanisms linking thiazolidinediones with the development or progression of bladder neoplasms have not been fully elucidated.7 How pioglitazone could increase the
risk of bladder cancer is therefore still being studied by the scientific community.
What are the risk factors for Bladder Cancer?
Risk factors of bladder cancer include smoking, exposure to certain chemicals, previous
cancer treatment, chronic bladder inflammation and a personal or family history of cancer.
Increasing age, male gender and being of white race are also known risk factors
What are the symptoms for Bladder Cancer?
Bladder cancer signs and symptoms may include blood in urine (haematuria), painful
urination and pelvic pain. Haematuria may appear as bright red or cola-coloured urine,
but sometimes may not show any change in the urine colour and may only be detected
during a microscopic examination of the urine in the laboratory.
When should you see a doctor?
Patients should contact their Doctor or healthcare professionals if they experience any
of the following signs or symptoms after starting pioglitazone, as these may be due to
bladder cancer:
• Blood or a red color in the urine,
• New or worsening urge to urinate
• Pain when urinating
Are there Pioglitazone-Containing Medicines on the Ghanaian Market?
- Yes there are pioglitazone-containing medicines registered by the FDA on the Ghanaian
market. Pioglitazone-containing medicines registered by the FDA have the following
brand names; Diavista, LG-Glizone, Nilgar, Pilgat and Piotex
What is the FDA Doing to regulate Pioglitazone-containing Medicines?
The
FDA has taken a number of steps listed below:
• Communication to healthcare professionals not to use pioglitazone as the first
choice for the treatment of Type 2 diabetes mellitus but used only in patients in
whom glycaemic targets cannot be reached with other oral therapies
(sulphonylureas and metformin), or in whom other therapies are contraindicated,
and to inform them about the potential risk factors.
• Companies marketing pioglitazone containing products are also requested to
indicate the potential adverse effect in the product package and also indicate those
in whom pioglitazone should not be used. Other countries such as the United
States of America and Canada have similar labelling requirements for pioglitazone
containing products.
• As part of the FDA’s Safety Monitoring Programme, companies marketing
pioglitazone are required to monitor and report adverse drug events to the FDA.
The FDA will continue to monitor and evaluate the scientific evidence and update
healthcare professionals and the public with any new information
What Should Patients do?
Patients should never take any medicine containing pioglitazone by themselves or upon
recommendation from friends or family. Patients who are concerned about the risk of
bladder cancer with the use of pioglitazone should talk to their Doctor or healthcare
professional.
How to Report Adverse Reactions to Pioglitazone and other products
Healthcare Professionals
• Complete Adverse Reaction Reporting Form and submit
Online : http://adr.fdaghana.gov.gh/
Mobile Number : 024 431 0297
Email : http://drug.safety@fdaghana.gov.gh.
Patients and Consumers
• Talk to your Doctor, Pharmacist, Nurse
SMS Short code : 4015
Mobile Number : 024 431 0297
Online : http://adr.fdaghana.gov.gh/patient.php
Email : drug.safety@fdaghana.gov.gh
References
1. Webmd Drugs and Medications, Pioglitazone HCL. Available at
http://www.webmd.com/drugs/2/drug-17406/pioglitazone-oral/details. Accessed on 4th
October 2017
2. Diabetes UK Pioglitazone and bladder cancer. December 2011 Available at
https://www.diabetes.org.uk/professionals/position-statements- reports/diagnosisongoing-management-monitoring/pioglitazone-and-bladder- cancer. Accessed on 4th October 2017.
3. American Cancer Society, What is Bladder Cancer. Available at
https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladdercancer.html.
Last Medical Review: January 26, 2016 Last Revised: May 23,
2016 Accessed on 3rd October 2017
4. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic
patients treated with pioglitazone: interim report of a longitudinal cohort study.
Diabetes Care 2011;34:916-22.
5. Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone Use and Risk of
Bladder Cancer and Other Common Cancers in Persons with Diabetes. JAMA
2015;314:265-77.
6. Filipova E, Uzunova K, Kalinov K, et al. Pioglitazone and the Risk of Bladder
Cancer: A Meta-Analysis. Diabetes Ther (2017) 8:705–726
7. Mayo Clinic, Bladder Cancer: Symptoms and Causes. Available at
Published 23rd June 2017 by Mayo
Clinic Staff. Accessed 3rd October 2017
