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Clinician’s Corner: THIAZOLIDINEDIONES (“glitazones”) (“TZD’s”)

THIAZOLIDINEDIONES (“glitazones”) (“TZD’s”)

  • Troglitazone (Rezulin) – removed from market in late 90’s due to drug induced hepatitis.
  • Pioglitazone (Actos)-Available strengths= 15, 30 and 45mg (available generically rather inexpensive)
  • Rosiglitazone (Avandia)= available strengths= 2,4,8mg

Mechanism of TZD’s:

  • work by increasing insulin sensitivity in fat and muscle tissue.
  • main action occurs in muscle tissue (~80%), where they increase insulin stimulated glucose disposal.
  • also affect the liver (~20%) where they decrease excessive liver glucose production.
  • can take 6 to 14 weeks to achieve maximum effects.
  • Caution using TZD’s with patients with heart failure. Liver function tests at baseline, then periodically, thereafter for both TZD’s.
  • TZD’s might also increase fracture risk especially in women.
  • Weight gain is possible—over a period of 6 months-1 year a 2-3 KG increase can occur and can be much higher.  Combination therapy with insulin can produce an even more dramatic weight gain.
  • Expected reduction: HgBA1c = (0.5- 1.4%) Fasting plasma glucose: 25-50mg/dl
  • Target population: insulin resistant, because this drug improves insulin sensitivity
  • Can be used alone, but usually add-on to Metformin

Actos ® (pioglitazone)  available generically. Very inexpensive. (released July 1999)

initial= 15-30mg  (usual=15-45mg)    ( max=30mg if combined with other agents)

  • Actos ® pioglitazone LOWERS triglycerides about 9% to 12% while Avandia® rosiglitazone can INCREASE triglycerides up to 15%.
  • Actos® pioglitazone also raises good cholesterol about 12% to 19% as compared to 8% to 19% for Avandia® rosiglitazone
  • Potential to cause bladder cancer. Avoid if potential for bladder cancer.

Avandia ® (rosiglitazone)   (released May 1999)- too expensive, as well as heart failure risk.

COMMENTS:

  • Caution using TZD’s with patients with heart failure.
  • TZD’s might also increase fracture risk especially in women.
  • Weight gain is possible—over a period of 6 months-1 year a 5 pound increase can occur, and can be much higher.  Combination therapy with insulin can produce an even more dramatic weight gain.
  • Actos (pioglitazone) might be a good option for our uninsured patients since it costs around
    $15.00/month

Patients should be aware of the signs of liver toxicity: nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice (skin and eyes), dark urine.