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

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Aim: 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 triglyceride (TG)-rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase-4 that has been
shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone-mediated
improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid
and incretin hormone levels as well as glucose homeostasis 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 glucagonlike
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 ß-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
ß-cell function.
Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Issue number4
Pages (from-to)366-373
Number of pages8
Publication statusPublished - Apr 2011

ID: 33725467