====== Rosiglitazone ======

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

→ [[endocrine:tzds:start|Thiazolidinediones (TZDs)]]

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===== 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.

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===== Clinical Effects =====

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

Unlike [[endocrine:tzds:pioglitazone|Pioglitazone]], rosiglitazone has minimal beneficial lipid effects.

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===== 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

→ [[cardio:heart_failure:start|Heart Failure Module]]

Rosiglitazone should be avoided in symptomatic heart failure.

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===== Adverse Effects =====

Common:

  * Weight gain
  * Peripheral edema
  * Fluid retention

Serious:

  * Worsening heart failure
  * Increased fracture risk
  * Rare hepatotoxicity

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===== Contraindications =====

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

Use caution in:

  * Osteoporosis
  * Patients with cardiovascular disease

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===== Rosiglitazone vs Pioglitazone =====

[[endocrine:tzds:pioglitazone|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.

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===== Current Clinical Role =====

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

  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[endocrine:biguanides:metformin|Metformin]]

Rosiglitazone is used infrequently in modern practice.

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===== 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

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===== Related =====

  * [[endocrine:tzds:start|Thiazolidinediones]]
  * [[endocrine:tzds:pioglitazone|Pioglitazone]]
  * [[cardio:heart_failure:start|Heart Failure Module]]