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.