A thiazolidinedione that enhances insulin sensitivity.

Brand name Actos.

A peroxisome proliferator-activated receptor γ agonist that ameliorates insulin resistance and improves glucose and lipid metabolism.

Decreases free fatty acids, the major mediator between the adipose tissue and insulin-sensitive organs such as skeletal muscle, beta cells, liver and fat.

Pioglitazone is a thiazolidinedione that acts as an agonist for peroxisome proliferator-activated receptor-gamma.

Decreases triglycerides, increases HDL and decreases the total/HDL cholesterol ratios in treated patients.

Works mainly at the level of the adipocyte acting on PPAR-x which is a transcription factor that is expressed in many tissues.

The thiazolidinedione pioglitazone may be added to metformin when hypoglycemia is especially undesirable.

Produces greater increases in HDL and reduces triglycerides to a greater degree than rosiglitazone.

Adverse effects include hypoglycemia, weight gain, and decrease hematocrit.

Can cause expansion of subcutaneous fat, adipocyte differentiation and proliferation.

Associated with fluid retention, and congestive heart failure.

Associated with a 2 fold increase in the risk of fracture, by decreasing osteoblast production.

Its use is contraindicated in patients with class III or IV heart failure.

In a case controlled study of 115,727 patients in the UK treated with diabetic found between 1988 and 2009 pounds and 83% increase in bladder cancer risk for patients who had ever taken pioglitazone:74 cases per 100,000 person-years(Azoulay L et al)..

In the above study patients taking the drug for two years or longer the bladder cancer rate was 88 cases per hundred thousand persons-years and 137 per hundred thousand in patients with a cumulative dose totaling 28,000 mg or more.

Use for more than 1 year may be associated with an increased risk of bladder cancer.

Drug should not be used in patients with active bladder cancer, and prior bladder cancer.

Pioglitazone administration in patients with type 2 diabetes increases insulin sensitivity by ~30%.


Similar to testosterone, pioglitazone reduces circulating free fatty acids and increases AMPK phosphorylation in skeletal muscle.


A 10-year analysis of patients with type 2 diabetes treated with pioglitazone (Actos) found no statistically significant increased risk of bladder cancer, either with any exposure or for long duration of use, in contrast to an earlier 5-year interim analysis that showed a significantly higher incidence of bladder cancer in long-term pioglitazone users.

Among 193,099 patients this drug was not associated with a statistically increased risk of bladder cancer, but an increased prostate and pancreatic cancer risks was associated with ever use of the drug (Lewis JD. Et al).

The 5-year study had found an increased risk among patients who took the drug for more than 2 years published in Diabetes Care, it included more than 193,000 patients, 30,173 of whom had been treated with pioglitazone.

A different analysis published in 2012, with about 5 years of follow-up, had confirmed an increased bladder cancer risk in pioglitazone users. And a meta-analysis of four randomized trials found an increased risk as well.

The new study was conducted by the University of Pennsylvania and Kaiser Permanente Northern California.

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