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In medicine, thiazolidinediones are "thiazoles with two keto oxygens. Members are insulin-sensitizing agents which overcome insulin resistance by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma)."[1] Thiazolidinediones are used for the treatment of diabetes mellitus type 2


Examples in include rosiglitazone and pioglitazone.

Avandia brand of rosiglitazone was approved by the Food and Drug Administration in the United States with a New Drug Application (NDA) in 1999.[2] A generic version was approved with a Abbreviated New Drug Application (ANDA) in 2004.[3]

Actos brand of pioglitazone was approved by the Food and Drug Administration in the United States with a New Drug Application (NDA) in 1999.[4] A generic version was approved with a Abbreviated New Drug Application (ANDA) in 2005.[5]


The initial choice of anti-diabetic drug has been compared in a randomized controlled trial which found "cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide."[6]

Pioglitazone, an insulin sensitizer, may reduce atherosclerosis compared to sulfonylureas which are insulin secretagogues.[7]

Adverse effects


Thiazolidinediones as a class may increase the risk of heart failure according to a meta-analysis of 20,191 patients in 7 trials.[8]

In addition, rosiglitazone[9], but not pioglitazone[10], may increase risk of death from cardiovascular causes according to larger meta-analyses that included unpublished trials.

Rosiglitazone is safer than pioglitazone according to a systematic review published in 2011.[11]


Long term use of thiazolidinediones may double the risk of fractures in women.[12]


  1. Anonymous (2023), Thiazolidinedione (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Drugs@FDA. U S Food and Drug Administration
  3. Drugs@FDA. U S Food and Drug Administration
  4. Drugs@FDA. U S Food and Drug Administration
  5. Drugs@FDA. U S Food and Drug Administration
  6. Kahn SE, Haffner SM, Heise MA, et al (2006). "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy". N. Engl. J. Med. 355 (23): 2427-43. DOI:10.1056/NEJMoa066224. PMID 17145742. Research Blogging.
  7. Nissen, S. E., Nicholls, S. J., Wolski, K., Nesto, R., Kupfer, S., Perez, A., et al. (2008). Comparison of Pioglitazone vs Glimepiride on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes: The PERISCOPE Randomized Controlled Trial. JAMA, 299(13), 1561-1573. doi: 10.1001/jama.299.13.1561.
  8. Lago RM, Singh PP, Nesto RW (September 2007). "Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials". Lancet 370 (9593): 1129–36. DOI:10.1016/S0140-6736(07)61514-1. PMID 17905165. Research Blogging.
  9. Nissen SE, Wolski K (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.". N Engl J Med 356 (24): 2457-71. DOI:10.1056/NEJMoa072761. PMID 17517853. Research Blogging. Review in: ACP J Club. 2007 Nov-Dec;147(3):66 Review in: Evid Based Med. 2007 Dec;12(6):169-70
  10. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE (2007). "Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.". JAMA 298 (10): 1180-8. DOI:10.1001/jama.298.10.1180. PMID 17848652. Research Blogging.
  11. Loke, Y. K.; C. S. Kwok, S. Singh (2011). "Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies". BMJ 342 (mar17 1): d1309-d1309. DOI:10.1136/bmj.d1309. ISSN 0959-8138. Retrieved on 2011-03-24. Research Blogging.
  12. Loke YK, Singh S, Furberg CD (January 2009). "Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis". CMAJ 180 (1): 32–9. DOI:10.1503/cmaj.080486. PMID 19073651. PMC 2612065. Research Blogging.