Overview
Pioglitazone is an antihyperglycemic used as an adjunct to diet, exercise, and other antidiabetic medications to manage type 2 diabetes mellitus. It is administered as a racemic mixture, though there is no pharmacologic difference between the enantiomers and they appear to interconvert in vivo with little consequence. The thiazolidinedione class of medications, which also includes rosiglitazone and troglitazone, exerts its pharmacological effect primarily by promoting insulin sensitivity and the improved uptake of blood glucose via agonism at the peroxisome proliferator-activated receptor-gamma (PPARγ). PPARs are ligand-activated transcription factors that are involved in the expression of more than 100 genes and affect numerous metabolic processes, most notably lipid and glucose homeostasis. Thiazolidinediones, including pioglitazone, have fallen out of favor in recent years due to the presence of multiple adverse effects and warnings regarding their use (e.g. congestive heart failure, bladder cancer) and the availability of safer and more effective alternatives for patients with type 2 diabetes mellitus.
Background
Pioglitazone is an antihyperglycemic used as an adjunct to diet, exercise, and other antidiabetic medications to manage type 2 diabetes mellitus. It is administered as a racemic mixture, though there is no pharmacologic difference between the enantiomers and they appear to interconvert in vivo with little consequence. The thiazolidinedione class of medications, which also includes rosiglitazone and troglitazone, exerts its pharmacological effect primarily by promoting insulin sensitivity and the improved uptake of blood glucose via agonism at the peroxisome proliferator-activated receptor-gamma (PPARγ). PPARs are ligand-activated transcription factors that are involved in the expression of more than 100 genes and affect numerous metabolic processes, most notably lipid and glucose homeostasis. Thiazolidinediones, including pioglitazone, have fallen out of favor in recent years due to the presence of multiple adverse effects and warnings regarding their use (e.g. congestive heart failure, bladder cancer) and the availability of safer and more effective alternatives for patients with type 2 diabetes mellitus.
Indication
Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also available in combination with metformin, glimepiride, or alogliptin for the same indication.
Associated Conditions
- Diabetes
- Diabetic Neuropathies
- Type 2 Diabetes Mellitus
Research Report
Pioglitazone: A Comprehensive Pharmacological and Clinical Review
1. Introduction to Pioglitazone
1.1 Overview and Classification
Pioglitazone (DrugBank ID: DB01132) is an oral antihyperglycemic agent belonging to the thiazolidinedione (TZD) class of medications.[1] Commonly marketed under brand names such as Actos® and Glustin™ [1], it is classified as a small molecule drug [1] with the Chemical Abstracts Service (CAS) number 111025-46-8. Pioglitazone is administered clinically as a racemic mixture; however, studies suggest that the enantiomers interconvert in vivo and possess minimal pharmacologic differences.[4]
1.2 Historical Context and Indication
Developed by Takeda Pharmaceuticals [1] and patented in 1985 [3], pioglitazone received initial regulatory approval from the U.S. Food and Drug Administration (FDA) in 1999 [1] and the European Medicines Agency (EMA) in 2000.[6] Its approved indication is as an adjunct to diet and exercise for the improvement of glycemic control in adult patients with type 2 diabetes mellitus (T2DM).[1] Pioglitazone addresses a fundamental pathophysiological defect in T2DM: insulin resistance.[2] Within the TZD class, it followed troglitazone, which was withdrawn due to hepatotoxicity, and was marketed alongside rosiglitazone.[2]
1.3 Initial Promise and Evolving Perceptions
Clinical Trials
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Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2009/06/23 | Not Applicable | Completed | |||
2009/06/23 | Phase 4 | Completed | |||
2009/06/23 | Phase 4 | Completed | |||
2009/06/18 | Phase 2 | Terminated | |||
2009/06/12 | Phase 1 | Completed | |||
2009/05/28 | Phase 3 | Completed | |||
2009/05/19 | Not Applicable | Completed | |||
2009/04/21 | Phase 3 | Completed | |||
2009/04/13 | Phase 4 | Terminated | |||
2009/03/24 | Not Applicable | Terminated |
FDA Drug Approvals
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PPB Drug Approvals
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