Contents

Search

pioglitazone (Actos)

Tradename: Actos. Genetic August 2012 [18] Indications: 1) adjunct to diet & exercise to improve diabetic control in patients with diabetes mellitus type 2 2) indicated as monotherapy or for use in combination with sulfonylurea, metformin or insulin 3) may reduce risk of cardiovascular events in diabetics (see PROactive study) 4) may reduce progression of coronary atherosclerosis (see PERISCOPE trial) 5) may reduce risk of subsequent cardiovascular event in patients with insulin resistance (but not diabetes) after ischemic stroke or transient ischemic attack (9 vs 12%) [24] 6) pioglitazone associated with reduced risk of dementia vs non-use in patients with diabetes mellitus type 2 (RR=0.84) [31] - risk of dementia reduction greater among patients with a history of ischemic heart disease or stroke before diabetes onset (RR=0.46) [31] 7) psoriasis (not FDA-approved use) [8] 8) may be useful in conjunction with imatinib for treatment of chronic myeloid leukemia [22] 9) treatment of nonalcoholic steatohepatitis (NASH) plus prediabetes or type 2 diabetes [26] Contraindications: (cautions) - heart failure (see recommendations for prescribing thiazolidinediones) - unclear whether pioglitazone results in net benefit or harm [23] - on list on medications to avoid [30] - heart failure & bone fractures cited Dosage: 1) start 15 mg PO QD 2) increase by 15 mg QD every 4 weeks 3) maximum dose: 45 mg QD 4) stop after 12 weeks if no benefit Tabs: 15, 30, 45 mg. Monitor: 1) ALT every 2 months for 1st year of therapy -> prior to initiation of therapy then every 3-6 months [9,15] 2) avoid if ALT > 2.5 x upper limit of normal 3) discontinue of ALT > 3 x upper limit of normal or if jaundice occurs Adverse effects: 1) hepatotoxicity less than troglitazone [6,9] 2) fluid retention & edema - may exacerbate heart failure [3,5,7] - may increase risk of heart failure [11] 3) no increase risk of myocardial infarction [11]; risk < rosiglitazone [12,14,17] 4) risk of osteoporosis & fractures in women [13] - increased risk of bone fractures (RR= 1.5) [29,30] 5) may increase risk of cancer - increased risk of bladder cancer (dose-dependent) [16,20] - increased risk of bladder cancer (RR=1.18) not significant after adjustment for potential confounders [21] - RR = 1.63 after 2 years of use [25] - not associated with excess risk for bladder cancer [27] - possible increased risk for bladder cancer [28] - increased risk for pancreatic cancer (RR=1.41-1.68) [21] - increased risk for prostate cancer (RR=1.13) [21] 6) increased risk of macular edema (RR = 6.5 at 1 year) [19] Mechanism of action: 1) thiazolidinedione 2) PPAR-gamma agonist 3) PPAR-gamma regulates transcription of insulin-responsive genes 4) increases peripheral uptake of glucose [23] 5) lowers insulin resistance [24] 6) decreases hepatic glucose production [23] 7) lowers serum triglycerides 9-12% [10] * PPAR: peroxisome proliferator-activated receptor

Interactions

drug interactions drug adverse effects (more general classes) monitor with thiazolidinediones (glitazones)

Related

metformin vs pioglitazone added to sulfonylurea Periscope trial peroxisome proliferator-activated receptor gamma; PPAR-gamma; nuclear receptor subfamily 1 group C member 3 (PPARG, NR1C3) PROactive study (PROspective pioglitAzone Clinical Trial In macroVascular Events) recommendations for prescribing thiazolidinediones (glitazones, TZDs) from the American Diabetic Association and the American Heart Association

General

peroxisome proliferator; PPAR agonist; PPAR gamma agonist thiazolidinedione; glitazone; TZD

Properties

MISC-INFO: elimination route LIVER KIDNEY

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Northern California Regional Drug Alert
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Prescriber's Letter 8(10):58 2001
  4. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  5. Prescriber's Letter 9(4):22 2002
  6. Journal Watch 22(8):60-61, 2002 May LD et al, Ann Intern Med 136:449, 2002
  7. Journal Watch 23(24):189, 2003 Delea TE et al, Diabetes Care 26:2983, 2003 PMID: 14578227
  8. Prescriber's Letter 11(8):41 2004 Avandia and Actos for Psoriasis Detail-Document#: 200802 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 11(9): 2004 Detail-Document#: 200903 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 12(8): 2005 Does Actos Improve Lipids Better than Avandia? Detail-Document#: 210310 (subscription needed) http://www.prescribersletter.com
  11. Lago RM et al. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: A meta-analysis of randomised clinical trials. Lancet 2007 Sep 29; 370:1129. PMID: 17905165 - Cleland JGF and Atkin SL. Thiazolidinediones, deadly sins, surrogates, and elephants. Lancet 2007 Sep 29; 370:1103. PMID: 17905146 - Montori VM et al. Patient-important outcomes in diabetes - time for consensus. Lancet 2007 Sep 29; 370:1104. PMID: 17905147
  12. Juurlink DN et al, Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ 2009;339:b2942 PMID: 19690342 http://www.bmj.com/cgi/content/full/339/aug18_2/b2942 - de Vries CS and Russell-Jones DL Rosiglitazone or pioglitazone in type 2 diabetes? BMJ 2009;339:b3076 PMID: 19690344 http://www.bmj.com/cgi/content/extract/339/aug18_2/b3076
  13. Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009 Jan 6;180(1):32-9. Epub 2008 Dec 10. PMID: 19073651 PMCID: PMC2612065 Free PMC article
  14. Tzoulaki I et al Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database BMJ 2009;339:b4731 PMID: 19959591 http://www.bmj.com/cgi/content/full/339/dec03_1/b4731
  15. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  16. FDA Medwatch: Posted 09/17/2010, 06/15/2011 Actos (pioglitazone): Ongoing Safety Review - Potential Increased Risk of Bladder Cancer http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226257.htm
  17. Loke YK et al Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies BMJ 2011; 342:d1309 PMID: 21415101 http://www.bmj.com/content/342/bmj.d1309.full - Montori VM and Shah ND What have we learnt from the rosiglitazone saga? BMJ 2011; 342:d1354 PMID: 21415102 http://www.bmj.com/content/342/bmj.d1354
  18. Prescriber's Letter 19(4): 2012 CHART: Anticipated Availability of First-Time Generics Detail-Document#: 280401 (subscription needed) http://www.prescribersletter.com - Physician's First Watch, Aug 27 2012 Massachusetts Medical Society http://www.jwatch.org - FDA News Release: Aug. 17, 2012 FDA approves first generic Actos to treat type 2 diabetes http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315951.htm
  19. Idris I et al Association Between Thiazolidinedione Treatment and Risk of Macular Edema Among Patients With Type 2 Diabetes Arch Intern Med. 2012;():1-7, June 2012 PMID: 22688528 http://archinte.jamanetwork.com/article.aspx?articleID=1182550 - Singh S and Segal JB Thiazolidinediones and Macular Edema: Comment on "Association Between Thiazolidinedione Treatment and Risk of Macular Edema Among Patients With Type 2 Diabetes" Arch Intern Med. 2012 Jun 11:1-2 PMID: 22688825
  20. Azoulay L et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: Nested case-control study. BMJ 2012 May 31; 344:e3645 PMID: 22653981
  21. 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 Jul 21;314(3):265-277 PMID: 26197187 http://jama.jamanetwork.com/article.aspx?articleid=2397834
  22. Prost S et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPAR-gamma agonists. Nature 2015 Sep 17; 525:380. PMID: 26331539 - Holyoake T and Vetrie D.Cancer: Repositioned to kill stem cells. Nature 2015 Sep 17; 525:328 PMID: 26331538
  23. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  24. Elia J, Hefner JE Pioglitazone for Secondary Prevention in Vascular Disease? Physician's First Watch, Feb 18, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Kernan WN et al Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. February 17, 2016 PMID: 26886418 http://www.nejm.org/doi/full/10.1056/NEJMoa1506930 - Semenkovich CF Insulin Resistance and a Long, Strange Trip. N Engl J Med. February 17, 2016 PMID: 26886417 http://www.nejm.org/doi/full/10.1056/NEJMe1600962
  25. Tuccori M et al Pioglitazone use and risk of bladder cancer: population based cohort study. BMJ 2016;352:i1541 PMID: 27029385 http://www.bmj.com/content/352/bmj.i1541 - Montori VM Selecting the right drug treatment for adults with type 2 diabetes. BMJ 2016;352:i1663 PMID: 27029501 http://www.bmj.com/content/352/bmj.i1663
  26. Cusi K, Orsak B, Bril F et al Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized, Controlled Trial. Ann Intern Med. Published online 21 June 2016 PMID: 27322798 http://annals.org/article.aspx?articleid=2529686 - Vilar-Gomez E, Adams LA Pioglitazone: An Addition to Our Toolbox for Patients With Diabetes and Nonalcoholic Steatohepatitis? Ann Intern Med. Published online 21 June 2016 PMID: 27322890 http://annals.org/article.aspx?articleid=2529687
  27. Korhonen P et al. Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: Retrospective cohort study using datasets from four European countries. BMJ 2016 Aug 16; 354:i3903 PMID: 27530399 Free PMC Article
  28. FDA Safety Alert. Dec 12, 2016 Pioglitazone-containing Medicines: Drug Safety Communication - Updated FDA Review, Increased Risk of Bladder Cancer. Includes Actos, Actoplus Met, Actoplus Met XR, Duetact, and Oseni. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm532772.htm - FDA Drug Safety Communication. Dec 12, 2016 Updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased risk of bladder cancer. http://www.fda.gov/Drugs/DrugSafety/ucm519616.htm
  29. Viscoli CM et al. Pioglitazone and risk for bone fracture: Safety data from a randomized clinical trial. J Clin Endocrinol Metab 2017 Mar; 102:914 PMID: 27935736 https://academic.oup.com/jcem/article-abstract/102/3/914/3061916/Pioglitazone-and-Risk-for-Bone-Fracture-Safety
  30. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  31. Monaco K Old Drug May Help Protect People With Diabetes Against Dementia. Those with history of ischemic heart disease or stroke saw greatest protection with pioglitazone. MedPage Today February 15, 2023 https://www.medpagetoday.com/neurology/dementia/103123 - Ha J, Choi DW, Kim, Kim KY, Nam CM, Kim E. Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke. Neurology. 2023. Feb 15 PMID: 36792375 https://n.neurology.org/content/early/2023/02/15/WNL.0000000000207069

Component-of

Actoplus Met (metformin, pioglitazone) alogliptin/pioglitazone (Oseni) glimepiride/pioglitazone (Duetact)