Rosiglitazone
Rosiglitazone (Avandia) is a thiazolidinedione PPAR-gamma agonist similar to pioglitazone. It improves insulin sensitivity but became notorious for a cardiovascular safety controversy that led to restrictions. Its use as a partitioning agent is discouraged given the risk profile.
01 Overview
Rosiglitazone activates PPAR-gamma to improve peripheral insulin sensitivity, much like pioglitazone, but with a less favourable lipid effect. A 2007 meta-analysis raising myocardial-infarction concerns led to severe restrictions and market withdrawal in Europe, later partly reversed.
Any physique interest in it as an insulin sensitizer is outweighed by the cardiovascular history, fluid retention and weight gain. It is included here for completeness rather than as a recommended agent.
02 Mechanism
Agonises PPAR-gamma in adipose tissue, promoting adipocyte differentiation, lipid uptake and glucose transporter expression, improving insulin sensitivity and lowering free fatty acids.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Diabetes | 4–8 mg/day | Oral | Once or twice daily; max 8 mg |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved insulin sensitivityEnhances peripheral glucose uptake via PPAR-gamma. | Lower fasting glucose and insulin | Clinical | |
| Lower circulating free fatty acidsSequesters fatty acids into adipose, reducing lipotoxicity. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Fluid retention and weight gainOedema and weight gain that can worsen heart failure. | Moderate | Common | Clinical | |
| Cardiovascular riskA debated increase in myocardial-infarction and heart-failure risk that drove regulatory restrictions. | Severe | Disputed / uncommon | Disputed |