Rosiglitazone
Rosiglitazone is a thiazolidinedione (TZD) that improves insulin sensitivity through activation of the PPAR-γ nuclear receptor.
Mechanism of Action
Rosiglitazone activates:
- Peroxisome proliferator-activated receptor gamma (PPAR-γ)
This leads to:
- Increased peripheral insulin sensitivity
- Reduced hepatic glucose production
- Improved glucose uptake in muscle and adipose tissue
It does NOT increase insulin secretion.
Low intrinsic hypoglycemia risk unless combined with insulin or secretagogues.
Clinical Effects
- Moderate HbA1c reduction
- Improved insulin resistance
- Slow onset of action (weeks)
Unlike Pioglitazone, rosiglitazone has minimal beneficial lipid effects.
Cardiovascular Controversy
Rosiglitazone was associated with:
- Possible increased myocardial infarction risk (early meta-analyses)
- Increased risk of heart failure due to fluid retention
Subsequent analyses led to removal of certain FDA restrictions, but use declined significantly.
Major concern:
- Fluid retention
- Worsening heart failure
Rosiglitazone should be avoided in symptomatic heart failure.
Adverse Effects
Common:
- Weight gain
- Peripheral edema
- Fluid retention
Serious:
- Worsening heart failure
- Increased fracture risk
- Rare hepatotoxicity
Contraindications
- NYHA Class III or IV heart failure
- Significant fluid overload
- Active liver disease
Use caution in:
- Osteoporosis
- Patients with cardiovascular disease
Rosiglitazone vs Pioglitazone
- Improves triglycerides
- More favorable lipid profile
- Also causes edema
- Possible bladder cancer concern
Rosiglitazone:
- Neutral or unfavorable lipid effects
- Historical MI controversy
- Similar fluid retention risk
Pioglitazone is generally preferred when a TZD is used.
Current Clinical Role
Due to cardiovascular concerns and availability of safer alternatives such as:
Rosiglitazone is used infrequently in modern practice.
Clinical Pearls
- PPAR-γ nuclear receptor agonist
- Improves insulin sensitivity
- Causes weight gain and edema
- Avoid in heart failure
- Largely replaced by newer cardioprotective agents