Abstract 14242: Sitagliptin Therapy Decreases Postprandial Levels of Both Intestinal and Hepatic Lipoproteins in Patients With Type 2 Diabetes
Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic TG-rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase IV that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes mainly through incretin hormone-mediated improvements in islet function. The hypothesis of the study was that treatment with sitagliptin will exert beneficial effects on postprandial lipemia by decreasing plasma concentrations of TG-rich lipoproteins, glucose, glucagon and free fatty acids as well as by increasing plasma levels of insulin and incretin hormones (intact GLP-1 and GIP) in patients with type 2 diabetes. Thirty six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1±6.4y and a BMI of 30.7±4.9 kg/m2) were recruited in this double-blind cross-over study using sitagliptin 100 mg/d or placebo for a 6-week period each, with a 6-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-hour period. Sitagliptin therapy significantly decreased the postprandial area under the curves (AUC) for plasma apoB (-5.1%, P=0.002), apoB-48 (-7.8%, P=0.03), TG (-9.4%, P=0.006), VLDL-C (-9.3%, P=0.001), free fatty acids (-7.6%, P=0.005) and glucose (-9.7%, P<0.0001). Furthermore, the postprandial AUCs for plasma GLP-1 (+67.8%, P<0.0001) and GIP (+67.3%, P<0.0001) were significantly increased following sitagliptin treatment 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 the HOMA index (-14.6%, P=0.01) and β-cell function (+32.3%, P=0.007). In conclusion, treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG-rich lipoproteins of both intestinal and hepatic origin, mainly through increased incretin hormone levels, reduced circulating plasma free fatty acid concentrations and improved insulin sensitivity and β-cell function.
- © 2010 by American Heart Association, Inc.