Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.[2]
Common side effects include headaches, muscle pains, inflammation of the throat, and swelling.[2] Serious side effects may include bladder cancer, low blood sugar, heart failure, and osteoporosis.[2] Use is not recommended in pregnancy or breastfeeding.[3] It is in the thiazolidinedione (TZD) class and works by improving sensitivity of tissues to insulin.[3]
Pioglitazone was patented in 1985, and came into medical use in 1999.[4] It is available as a generic medication.[3] In 2023, it was the 133rd most commonly prescribed medication in the United States, with more than 4million prescriptions.[5][6] It was withdrawn in France and Germany in 2011.[7][8]
Medical uses
Pioglitazone is used to lower blood glucose levels in type 2 diabetes either alone or in combination with sulfonylurea, metformin, or insulin.[9] The effects of pioglitazone have been compared in a Cochrane systematic review to that of other blood sugar lowering-medicine, including metformin, acarbose, and repaglinide, as well as with appropriate diet and exercise, not showing any benefit in reducing the chance of developing type 2 diabetes in people at risk.[10] It did, however, show reduction of risk of developing type 2 diabetes when compared to a placebo or to no treatment.[10] These results should be interpreted considering that most of the data of the studies included in this review were of low or very-low certainty.
While pioglitazone does decrease blood sugar levels, the main study that looked at the medication found no difference in the main cardiovascular outcomes that were looked at.[11] The secondary outcome of death from all causes, myocardial infarction, and stroke were lower.[11]
Contraindications
Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of the components of its pharmaceutical forms. It is ineffective and possibly harmful in diabetes mellitus type 1 and diabetic ketoacidosis.[9] Its safety in pregnancy, lactation (breastfeeding) and people under 18 is not established.[9]
Given previous experiences with the related drug troglitazone, acute diseases of the liver are regarded as a contraindication for pioglitazone.
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.[14]
The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose.
Pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate 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.
Chronic administration of the drug has led to occasional instances of cholestatic hepatitis, reversible upon drug discontinuation.[15]
Drug interactions
Combination with sulfonylureas or insulin increase the risk of hypoglycemia.[23]
Treatment with pioglitazone decreases the effectiveness of oral contraceptions containing ethinyl estradiol and norethindrone.[24]
Mechanism of action
Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α.[25][26] It modulates the transcription of the genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver, and reduces quantity of glucose and glycated hemoglobin in the bloodstream.
Since 2004, pioglitazone and other active TZDs have been shown to bind to the outer mitochondrial membrane protein mitoNEET with affinity comparable to that of pioglitazone for PPARγ.[27][28]
Leriglitazone is a metabolite.
Society and culture
Economics
In 2008, it generated the tenth-highest amount of money for a medication in the U.S. in 2008, with sales exceeding $2.4 billion.[30]
To 2020, no study has examined the socioeconomic effects of utilization of pioglitazone.[10]
Brand names
Pioglitazone is marketed as Actos in the United States, Canada, the UK and Germany, Glustin in the European Union, Glizone and Pioz in India by Zydus Cadila and USV Limited, respectively, and Zactos in Mexico by Takeda Pharmaceuticals. On 17 August 2012, the US FDA announced its approval of the first generic version of Actos.[31]
Research
Psychiatry
Bipolar disorder
Pioglitazone has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder.[32] However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of pioglitazone in the treatment of bipolar depression.[32]
Major depression
There is research that suggests that pioglitazone may be useful for treating major depression.[33]
Bipolar disorder
See also
- Abdominal obesity (pioglitazone mentioned)
References
- Actos EPAR European Medicines Agency (EMA), 13 October 2000, retrieved 27 August 2024^
- Pioglitazone Hydrochloride Monograph for Professionals Drugs.com, American Society of Health-System Pharmacists, retrieved 3 March 2019^
- British national formulary: BNF 76 Pharmaceutical Press, 2018^