Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

Methods: Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 +/- 6.4 years and a body mass index of 30.7 +/- 4.9 kg/m2) were recruited in this double-blind cross-over study using sitagliptin 100 mg/day or placebo for a 6-week period each, with a 4-week washout period between the two phases. At the end of each phase of treatment, patients underwent an oral lipid tolerance test providing 35 g of fat per m2 of body surface area and blood samples were taken over an 8-h period. Results: Sitagliptin therapy significantly decreased the postprandial area under the curves (AUCs) for plasma apolipoprotein (apo)B (-5.1%, p = 0.002), apoB-48 (-7.8%, p = 0.03), TG (-9.4%, p = 0.006), very low-density lipoprotein (VLDL)-cholesterol (-9.3%, p = 0.001), free fatty acids (FFAs) (-7.6%, p = 0.005) and glucose (-9.7%, p < 0.0001). Furthermore, the postprandial AUCs for plasma intact glucagon-like peptide-1 (+67.8%, p < 0.0001) and glucose-dependent insulinotropic polypeptide (+67.3%, p < 0.0001) were significantly increased following treatment with sitagliptin, whereas the AUC for plasma glucagon was reduced by -9.7% (p = 0.001) with no significant changes in the AUCs for plasma insulin and C-peptide. Sitagliptin therapy also improved homeostasis model assessment (HOMA) index for insulin resistance (-14.6%, p = 0.01) and beta-cell function (+32.3%, p = 0.007). Conclusions: Treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG-rich lipoproteins of both intestinal and hepatic origin, most likely by increasing incretin hormone levels, reducing circulating plasma FFA concentrations and improving insulin sensitivity and beta-cell function.