Rosiglitazone

Rosiglitazone is a thiazolidinedione (TZD) that improves insulin sensitivity through activation of the PPAR-γ nuclear receptor.

→ Thiazolidinediones (TZDs)

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.

• Moderate HbA1c reduction
• Improved insulin resistance
• Slow onset of action (weeks)

Unlike Pioglitazone, rosiglitazone has minimal beneficial lipid effects.

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

→ Heart Failure Module

Rosiglitazone should be avoided in symptomatic heart failure.

Common:

• Weight gain
• Peripheral edema
• Fluid retention

Serious:

• Worsening heart failure
• Increased fracture risk
• Rare hepatotoxicity

• NYHA Class III or IV heart failure
• Significant fluid overload
• Active liver disease

Use caution in:

• Osteoporosis
• Patients with cardiovascular disease

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.

Due to cardiovascular concerns and availability of safer alternatives such as:

• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Metformin

Rosiglitazone is used infrequently in modern practice.

• PPAR-γ nuclear receptor agonist
• Improves insulin sensitivity
• Causes weight gain and edema
• Avoid in heart failure
• Largely replaced by newer cardioprotective agents

• Thiazolidinediones
• Pioglitazone
• Heart Failure Module