Editing Pioglitazone (section)

==Side effects==
A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given [[rosiglitazone]] compared with those given metformin or glyburide. The information was based on data from the ADOPT trial. Following release of this statement, [[Takeda Pharmaceutical Company]], the developer of pioglitazone (sold as Actos in many markets) admitted that it has similar implications for female patients.<ref name='Takeda, 2007'>{{cite web | url = https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM153896.pdf | title = Observation of an Increased Incidence of Fractures in Female Patients Who Received Long-Term Treatment with ACTOSO (pioglitazone HOI) Tablets for Type 2 Diabetes Mellitus | access-date = 4 April 2012 | work = Takeda | publisher = [[Food and Drug Administration]] | date = March 2007 | archive-url = https://web.archive.org/web/20120516103123/http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM153896.pdf | archive-date = 16 May 2012 | url-status = dead }}</ref>

The risk of [[hypoglycemia]] is low in the absence of other drugs that lower blood glucose.{{medcn|date=February 2020}}

Pioglitazone can cause [[water retention (medicine)|fluid retention]] and peripheral [[edema]]. As a result, it may precipitate [[Heart failure|congestive heart failure]] (which worsens with fluid overload in those at risk). It may cause [[anemia]]. Mild weight gain is common due to increase in subcutaneous [[adipose tissue]]. In studies, patients on pioglitazone had an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.{{medcn|date=February 2020}}

Chronic administration of the drug has led to occasional instances of [[cholestatic hepatitis]], reversible upon drug discontinuation.<ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1271–2 }}</ref>

On 30 July 2007, an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of "myocardial ischemic events" when compared to placebo, but when compared to other diabetes drugs, there was no increased risk. Pioglitazone is currently being reviewed. A [[meta-analysis]] released subsequently showed that pioglitazone reduced the risk of ischemic cardiac events rather than increased the risk, but increased [[Heart failure|CHF]].<ref>{{cite journal | vauthors = Lincoff AM, Wolski K, Nicholls SJ, Nissen SE | title = Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials | journal = JAMA | volume = 298 | issue = 10 | pages = 1180–8 | date = September 2007 | pmid = 17848652 | doi = 10.1001/jama.298.10.1180 }}</ref>

A 2020 Cochrane systematic review assessed occurrence of adverse effects with use of pioglitazone, but was not able to reach any conclusions due to insufficient data on included studies.<ref name=":0" />

===Bladder cancer===
On 9 June 2011, the [[French Agency for the Safety of Health Products]] decided to withdraw pioglitazone due to high risk of [[bladder cancer]].<ref>{{cite web | title = L'antidiabétique Actos retiré du marché | trans-title = Actos antidiabetic withdrawn from the market | language = fr | url = http://www.lefigaro.fr/flash-actu/2011/06/09/97001-20110609FILWWW00505-info-le-figaro-lantidiabetique-actos-retire-du-marche.php | work = Le Figaro | date = 9 June 2011 | access-date = 9 June 2011 | archive-date = 12 June 2011 | archive-url = https://web.archive.org/web/20110612001536/http://www.lefigaro.fr/flash-actu/2011/06/09/97001-20110609FILWWW00505-info-le-figaro-lantidiabetique-actos-retire-du-marche.php | url-status = live }}</ref> This suspension was based on the results of an epidemiological study conducted by the French National Health Insurance. According to the results of the epidemiological study, the French agency found that patients, who were taking Actos for a long time to aid in type 2 diabetes mellitus, significantly increased risk of bladder cancer compared with patients who were taking other diabetes medications.<ref>{{cite web | vauthors = Alam II | date = 1 January 2012 | url = http://www.medical-reference.net/2011/12/france-and-germany-suspended-use-of.html | title = France and Germany Suspended Use of Actos for Bladder Cancer Risk | work = Medical-Reference | access-date = 27 August 2012 | archive-date = 2 September 2012 | archive-url = https://web.archive.org/web/20120902222645/http://www.medical-reference.net/2011/12/france-and-germany-suspended-use-of.html | url-status = live }}</ref> On 10 June 2011, Germany's [[Federal Institute for Drugs and Medical Devices]] also advised doctors not to prescribe the medication until further investigation of the cancer risk had been conducted.<ref>{{cite news | url=https://www.reuters.com/article/takeda-germany-idUSL3E7HA0X920110610 | work=Reuters |  vauthors = Topham J | title=UPDATE 2-Germany joins France in suspending top Takeda drug | date=10 June 2011 | access-date=1 July 2017 | archive-date=13 November 2015 | archive-url=https://web.archive.org/web/20151113074307/http://www.reuters.com/article/2011/06/10/takeda-germany-idUSL3E7HA0X920110610 | url-status=live }}</ref>

On 15 June 2011, the U.S. [[Food and Drug Administration|FDA]] announced that pioglitazone use for more than one year may be associated with an increased risk of bladder cancer, and two months later the label was updated with an additional warning about this risk.<ref>{{cite web | title = FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines | date = 4 August 2011 | url = https://www.fda.gov/Drugs/DrugSafety/ucm266555.htm | publisher = U.S. [[Food and Drug Administration]] (FDA) | access-date = 16 December 2019 | archive-date = 24 April 2019 | archive-url = https://web.archive.org/web/20190424012237/https://www.fda.gov/Drugs/DrugSafety/ucm266555.htm | url-status = dead }}</ref><ref name="FDA safety">{{cite web | title=Update to ongoing safety review of Actos | website=U.S. Food and Drug Administration | date=18 June 2019 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-update-ongoing-safety-review-actos-pioglitazone-and-increased-risk | access-date=8 November 2020 | archive-date=28 September 2020 | archive-url=https://web.archive.org/web/20200928032722/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-update-ongoing-safety-review-actos-pioglitazone-and-increased-risk | url-status=dead }}</ref>

A 2017 meta-analysis found no difference in the rates of bladder cancer attributed to pioglitazone.<ref>{{cite journal | vauthors = Filipova E, Uzunova K, Kalinov K, Vekov T | title = Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis | journal = Diabetes Therapy | volume = 8 | issue = 4 | pages = 705–726 | date = August 2017 | pmid = 28623552 | pmc = 5544610 | doi = 10.1007/s13300-017-0273-4 }}</ref>