Medicine & USMLE

TZDs (Thiazolidinediones)

Diabetes Drugs (New)
  1. DPP-4 Inhibitors
  2. GLP-1 Analogs
  3. Insulin Overview
  4. Insulin Preparations
  5. Metformin (Biguanides)
  6. TZDs (Thiazolidinediones)
  7. Sulfonylureas
  8. Meglitinides
  9. SGLT2 Inhibitors
  10. Alpha-Glucosidase Inhibitors
  11. Pramlintide (Amylin Analogs)


TZDs, short for Thiazolidinediones, are a class of drugs with names that end in -glitazone, including pioglitazone and rosiglitazone. These medications are clinically used to treat diabetes mellitus, especially type 2 diabetes mellitus. 

Mechanistically, these drugs work by activating PPAR-gamma, which is a nuclear receptor. This has several downstream effects, including increasing levels of adiponectin, and increasing insulin sensitivity.
Side effects common to all TZDs include edema and fluid retention. While these drugs typically do not cause hypoglycemia as a side effect, they can cause weight gain in patients. TZDs also have delayed onset for several weeks, which means that patients may need to wait some time until they see an effect. Taking TZDs can increase the risk of bone fractures in patients. In addition, these drugs can either cause or worsen existing cases of heart failure.

In addition to the side effects common to all TZDs, the use of rosiglitazone is specifically thought to increase the risk of heart attacks and cardiovascular death.

Key Points

  • Thiazolidinediones (TZDs)
    • Drug Names
      • -glitazone
        • pioglitazone
        • rosiglitazone
    • Mechanisms
      • Activate PPAR-gamma (a nuclear receptor)
        • Stands for peroxisome proliferator-activated receptor gamma (contrast vs. Fibrates which affect PPAR-alpha)
        • Changes transcription of genes
        • Increase insulin sensitivity
          • Upregulates insulin-dependent GLUT-4 glucose transporter expression, which increases insulin sensitivity in peripheral tissues
        • Increase adiponectin
          • Cytokine secreted by fat that regulates insulin sensitivity, glucose metabolism, and fatty acid storage
    • Clinical Use
      • Treats diabetes mellitus
    • Side Effects
      • Edema (fluid retention)
        • Can precipitate heart failure (decompensation)
      • Weight gain
        • Mainly secondary to fluid retention
        • Also possibly due to increased adipocyte storage
      • Increased risk of bone fractures
        • TZDs affect differentiation of mesenchymal stem cells, increasing adipogenesis at expense of decreased osteoblast levels
        • Decreased osteoblasts leads to decreased bone density
      • Delayed onset of action (several weeks)
        • Since effect is dependent on changing expression of genes and resultant protein formation
      • Cardiotoxicity (rosiglitazone)
        • Increased risk of myocardial infarction and cardiovascular death
        • An increase in the risk of death from cardiovascular causes that had borderline significance [source]
      • No hypoglycemia
        • Since these drugs increase insulin sensitivity and do not directly release insulin