The effect of metformin and rosiglitazone on postprandial lipid metabolism in obese insulin-resistant subjects

Introduction: Obese insulin-resistant individuals exhibit a dyslipidaemia due to raised levels of both hepatically and intestinally derived lipoproteins. However, little is known about the related dysregulation of intestinally derived lipoproteins. We examined whether the insulin-sensitizing agents, metformin and rosiglitazone, improve intestinal lipoprotein metabolism in obese insulin-resistant individuals. Methods: Thirty male obese (body mass index > 26; waist circumference > 100 cm) insulin-resistant [homeostasis model assessment (HOMA) score > 2.0] subjects were randomized to either a metformin (1 g bd), rosiglitazone (4 mg bd) or control treatment group for a period of 8 weeks. Fasting and postprandial lipid metabolism was studied before and after the intervention period. Results: Metformin and rosiglitazone both significantly improved insulin sensitivity, but this was not paralleled by improvement in dyslipidaemia. With rosiglitazone relative to control there was a significant (p < 0.05) increase in the area under the apolipoprotein (apo) B48 curve following the oral fat load and a decrease in the ratio of triglyceride to apo B48 levels postprandially following rosiglitazone treatment. Conclusion: In obese insulin-resistant subjects metformin and rosiglitazone both improve insulin sensitivity, as measured by HOMA, without improvement in lipid metabolism. Rosiglitazone may have a detrimental effect on chylomicron metabolism by an increase in postprandial apo B48 levels, and this requires further investigation.