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ThiazolidinedioneAka: Glitazone, Rosiglitazone, Avandia, Pioglitazone, Actos, Troglitazone, Rezulin

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  1. Indications
    1. Oral Hypoglycemic for Type II Diabetes Mellitus
      1. Second line agent
      2. Add to other Oral Hypoglycemic agents
    2. Diabetes with coronary Vasospastic Angina pectoris
      1. Murakami (1999) Am J Cardiol 84:92
    3. Insulin Resistance Syndromes (experimental)
      1. Polycystic Ovary Syndrome
    4. Psoriasis (experimental)
      1. Thiazolidinediones activate PPARs
        1. Peroxisome proliferator-activated receptors (PPARs)
      2. PPARs have antiinflammatory activity in Psoriasis
        1. Ellis (2000) Arch Dermatol 136(5):609
  2. Contraindications
    1. Liver disease (ALT > 2.5x upper limit of normal)
    2. CHF NYA Class III or Class IV Heart Failure
  3. Mechanism
    1. Thiazolidinedione derivative
    2. Acts at liver, skeletal muscle and fat cells
    3. Activates peroxisome proliferator activated receptors
      1. Receptors known as PPARS
      2. Reduces Insulin Resistance
      3. May independently reduce cardiovascular risk
      4. Increases glucose uptake
      5. Decreases hepatic glucose output
    4. Shifts fat deposition from visceral to subcutaneous
    5. Decreases free fatty acid levels
  4. Adverse Effects
    1. Hepatotoxicity and Liver Failure
      1. Associated with Troglitazone use
      2. Troglitazone removed from U.S. market in March 2000
      3. Rosiglitazone and Pioglitazone may also cause
      4. Follow Liver Function Tests closely
        1. Especially follow in first year
      5. References
        1. May (2002) Ann Intern Med 136:449
    2. Fluid retention
      1. Congestive Heart Failure risk (see below)
      2. Peripheral edema (in 3-5% of patients)
      3. Moderate weight gain (1-3 kg)
      4. Mild Anemia
    3. Variable lipid effects
      1. Pioglitazone (Actos)
        1. Lowers Triglycerides by 9-12%
        2. Raises HDL Cholesterol by 12-19%
      2. Rosiglitazone (Avandia):
        1. RAISES Triglycerides by 15%
        2. Raises HDL Cholesterol by 8-19%
        3. Raises LDL Cholesterol
      3. References
        1. (2005) Prescriber's Letter 12(8):43
    4. Increased LDL Cholesterol and HDL Cholesterol
    5. Risks of adverse effects compounded with Insulin
      1. Weight gain (3-4 kg)
      2. Edema (8-10% of cases)
      3. Congestive Heart Failure
        1. Observe patients with CHF risk closely
      4. Hypoglycemia risk
    6. Possible decreased bone density
      1. May be specific to Pioglitazone (Actos)
    7. Cardiovascular risk
      1. Rosiglitazone (Avandia) appears to increase CAD risk
      2. Pioglitazone (Actos) may slightly decrease CAD risk
  5. Preparations
    1. Protocol
      1. Discontinue if no improvement in 8-12 weeks
    2. Rosiglitazone (Avandia)
      1. Initial: 4 mg PO qd (or 2 mg PO bid)
      2. Maximum: 8 mg per day (4 mg if on Insulin)
    3. Pioglitazone (Actos) - preferred due to vascular disease risk
      1. Initial: 15 to 30 mg PO qd
      2. Maximum: 45 mg per day
    4. Conversion between agents
      1. Rosiglitazone 2 mg is equivalent to Pioglitazone 15 mg
      2. Rosiglitazone 4 mg is equivalent to Pioglitazone 30 mg
      3. Rosiglitazone 8 mg is equivalent to Pioglitazone 45 mg
  6. Pharmacokinetics
    1. Hepatic metabolism by Cytochrome P450: CYP2C8
  7. Monitoring
    1. Liver Function Tests
      1. Initial: Baseline and in 6-12 weeks
      2. Later: Every 6 months
    2. Do not start medication if LFTs > 2.5x normal
    3. Stop medication if LFTs >3x normal
    4. Follow weight for weight gain (esp. if CHF risk)
  8. Efficacy
    1. Add to Metformin, Sulfonylurea - delays Insulin need
    2. References
      1. Aljabri (2004) Am J Med 116:230
      2. Dailey (2004) Am J Med 116:223
  9. Cost
    1. Expensive! (Up to $175 to $192 per month)
  10. References
    1. (1999) Med Lett Drugs Ther 41(1059):71
    2. Krische (2000) West J Med 173:54
    3. Schwartz (1998) N Engl J Med 338:861
    4. Saltiel (1996) Diabetes 45:1661

pioglitazone (C0071097)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishpioglitazone, PIOGLITAZONE PREPARATION
Spanishpioglitazona
CreditsDerived from the NIH UMLS (Unified Medical Language System)


troglitazone (C0245514)

Definition (NCI)A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue.
Definition (PDQ)An orally-active thiazolidinedione with antidiabetic and hepatotoxic properties and potential antineoplastic activity. Troglitazone 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. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42706&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42706&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1522" NCI Thesaurus)
Definition (NCI)An orally-active thiazolidinedione with antidiabetic and hepatotoxic properties and potential antineoplastic activity. Troglitazone 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. (NCI04)
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishtroglitazone, TROGLITAZONE PREPARATION
Spanishtroglitazona
CreditsDerived from the NIH UMLS (Unified Medical Language System)


rosiglitazone (C0289313)

Definition (NCI)A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones.
Definition (NCI)An orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Rosiglitazone 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. (NCI04)
Definition (CSP)peroxisome proliferator activated receptor agonist; reduces lipid availability; improves insulin action and glucoregulation.
Definition (PDQ)An orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Rosiglitazone 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. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37793&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37793&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2583" NCI Thesaurus)
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishROS, rosiglitazone, ROSIGLITAZONE PREPARATION
Spanishrosiglitazona
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Rezulin (C0701265)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishParke Davis brand of troglitazone, Rezulin
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Actos (C0875954)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishActos, Eli Lilly brand of pioglitazone hydrochloride, Takeda brand of pioglitazone hydrochloride
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Avandia (C0875967)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishAvandia, Glaxo Wellcome brand of rosiglitazone maleate, GlaxoSmithKline brand of rosiglitazone maleate, SmithKline Beecham brand of rosiglitazone maleate
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Thiazolidinediones (C1257987)

Definition (MSH)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).
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishGlitazones, Thiazolidinedione, Thiazolidinediones
Spanishtiazolidinadiona, tiazolidinediona
CreditsDerived from the NIH UMLS (Unified Medical Language System)



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