II. Indications
- Pioglitazone is preferred of the Glitazones
- Vascular disease risk increase with Rosiglitazone
-
Oral Hypoglycemic for Type II Diabetes Mellitus
- Second line agent (although falling out of favor in 2012 due to risks)
- Add to other Oral Hypoglycemic agents
- Diabetes with coronary Vasospastic Angina pectoris
- Insulin Resistance Syndromes (experimental)
-
Psoriasis (experimental)
- Thiazolidinediones activate PPARs
- Peroxisome proliferator-activated receptors (PPARs)
- PPARs have antiinflammatory activity in Psoriasis
- Thiazolidinediones activate PPARs
III. Contraindications
- Type 1 Diabetes Mellitus
- Liver disease (ALT > 2.5x upper limit of normal)
- CHF NYA Class III or Class IV Heart Failure
- Osteoporosis or Osteopenia
- Bladder Cancer
IV. Precautions
- CHF exacerbation risk (and contraindicated for NYHA Class III or IV) for ALL Glitazones (FDA Black Box warning)
V. Mechanism
- Thiazolidinedione derivative
- Primary mechanism: Increases peripheral tissue Insulin sensitivity
- Secondary mechanism: Decreases hepatic Glucose production
- Acts at liver, skeletal Muscle and fat cells
- Activates peroxisome proliferator activated receptors
- Receptors known as PPARS
- Reduces Insulin Resistance
- May independently reduce Cardiovascular Risk
- Increases Glucose uptake
- Decreases hepatic Glucose output
- Shifts fat deposition from visceral to subcutaneous
- Decreases free Fatty Acid levels
VI. Medications
- Pioglitazone (Actos) 15 mg, 30 mg, 45 mg
VII. Dosing
- Protocol
- Discontinue if no improvement in diabetes control within 8 to 12 weeks
- Dosing
- Start: 15 to 30 mg orally daily for the first 3 months
- Maximum: 45 mg per day
VIII. Adverse Effects
- Hepatotoxicity and Liver Failure
- Associated with Troglitazone use
- Troglitazone removed from U.S. market in March 2000
- Rosiglitazone and Pioglitazone may also cause this
- Follow Liver Function Tests closely
- Especially follow in first year
- References
- Fluid retention
- Congestive Heart Failure risk (see below)
- Peripheral Edema (in 3-5% of patients)
- Moderate weight gain (1-3 kg)
- Mild Anemia
- Variable lipid effects
- Pioglitazone (Actos)
- Lowers Triglycerides by 9-12%
- Raises HDL Cholesterol by 12-19%
- Rosiglitazone (Avandia):
- RAISES Triglycerides by 15%
- Raises HDL Cholesterol by 8-19%
- Raises LDL Cholesterol
- References
- (2005) Prescriber's Letter 12(8):43
- Pioglitazone (Actos)
- Risks of adverse effects (compounded when combined with Insulin)
- Weight gain (3-4 kg)
- Edema (8-10% of cases)
- Congestive Heart Failure
- Observe patients with CHF risk closely
- Hypoglycemia risk
-
Fracture Risk and Decreased Bone Density (Osteoporosis risk)
- Class effect
- Odds Ratio approaches 2.5 for Glitazone use >8 months
- (2008) Arch Intern Med 168:820-5 [PubMed]
-
Cardiovascular Risk
-
Rosiglitazone (Avandia) appears to increase CAD risk
- No longer recommended as a first-line agent
- Pioglitazone (Actos) may slightly decrease CAD risk
- Atherosclerosis may be slowed by Actos
- Nissen (2008) JAMA 299(13):1561-73 [PubMed]
-
Rosiglitazone (Avandia) appears to increase CAD risk
-
Bladder Cancer risk
- Risk of up to 11 per 10,000 cases per patients taking Pioglitazone (actos) >1 year
- Mamtani (2012) J Natl Cancer Inst 104 (18): 1411-1421 [PubMed]
IX. Pharmacokinetics
- Hepatic metabolism by Cytochrome P450: CYP2C8
X. Monitoring
-
Liver Function Tests
- Initial: Baseline and in 6-12 weeks
- Later: Every 6 months
- Do not start medication if LFTs > 2.5x normal
- Stop medication if LFTs >3x normal
- Follow weight for weight gain (esp. if CHF risk)
XI. Efficacy
- Lowers Hemoglobin A1C 0.5 to 1.5%
- Delays Insulin need when added to Metformin, Sulfonylureas
XII. Safety
- Unknown Safety in pregnancy
- Avoid in Lactation
XIII. Resources
- Pioglitazone (DailyMed)
Images: Related links to external sites (from Bing)
Related Studies
| pioglitazone (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PIOGLITAZONE HCL 15 MG TABLET | Generic | $0.08 each |
| PIOGLITAZONE HCL 30 MG TABLET | Generic | $0.12 each |
| PIOGLITAZONE HCL 45 MG TABLET | Generic | $0.14 each |
| PIOGLITAZONE-METFORMIN 15-500 | Generic | $0.29 each |
| PIOGLITAZONE-METFORMIN 15-850 | Generic | $0.39 each |
Ontology: pioglitazone (C0071097)
| Definition (NCI_NCI-GLOSS) | A drug that is used to treat type 2 diabetes and is being studied in the prevention of head and neck cancer. It may be able to stop leukoplakia (a condition affecting the mouth ) from developing into cancer. It is a type of thiazolidinedione. |
| Definition (NCI) | An orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C060836 |
| SnomedCT | 326058001, 395828009 |
| LNC | LP171629-1 |
| English | 5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione, pioglitazone, pioglitazone [Chemical/Ingredient], PIOGLITAZONE, Pioglitazone (product), Pioglitazone (substance), Pioglitazone |
| Spanish | pioglitazona (producto), pioglitazona (sustancia), pioglitazona |
Ontology: Actos (C0875954)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C060836 |
| English | Actos, pioglitazone (Actos), actos, acto, Eli Lilly brand of pioglitazone hydrochloride, Takeda brand of pioglitazone hydrochloride |
