TZDs

insulin sensitizers/insulin enhancers

direct stimulation of PPAR-gamma --> inc in GLUT-4 on cell surface --> increase in insulin uptake in muscle and adipose and dec in hepatic glucose production

MOAs

• metformin: 1-dec hepatic glucose output; 2-better insulin sensitivity in muscle and adipose
• TZD: 1-better insulin sensitivity in muscle and adipose; 2-dec hepatic glucose output

• hepatic metabolism
• elimination in urine (more) and feces (less)

• hepatic metabolism
• eliminated in feces

• dec in BG seen in 2-4 wks
• full effects in up to 12 wks
• perseverance of effect for 1-2 yrs

• rosiglitazone: inc cholesterol, LDL, HDL
• pioglitazone: inc HDL, dec TGs

• Heart failure (especially rosiglitazone)
• - fluid retention

MI (rosiglitazone) - can only get with distribution program

• heart failure inc risk (lowest dose if in Class 2 HF)
• macular edema (use with caution in pts with edema)
• more bone fracture in women
• resumption of ovulation in perimenopausal anovulatroy women
• bladder cancer

• no signs of hepatotoxicity
• rosi: MI, death from CV causes
• pio: bladder cancer
• weight gain (dose dependent)
• edema (dose dependent; more common with insulin)
• dec in Hbg and Hct (bc of fluid imbalance)
• resumption of ovulation
• bone fracture
• macular edema

• LFTs b4 starting
• don't start if ALT > 2.5x upper limit
• get LFT's at first signs of hepatic dysfuntion (fatigue, anorexia, nausea, vomiting, ab pain, dark urine, jaundice) -->if continues, d/c