Sitagliptin Improves the Impaired Acute Insulin Response during a Meal Tolerance Test in Japanese Patients with Type 2 Diabetes Mellitus: A Small-Scale Real-World Study

Abstract

IntroductionSeveral studies have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors improve insulin secretion during oral glucose tolerance tests. However, the effects of DPP-4 inhibitors on impaired acute insulin responses in the postprandial state in real-world settings are unknown. Therefore, we evaluated the effects of sitagliptin on the acute insulin responses in Japanese patients with type 2 diabetes mellitus (T2DM) using meal tolerance tests.MethodsTwenty-one patients with T2DM were given a test meal (460 kcal), and plasma glucose and insulin were measured at 0, 30, 60, 120, and 180 min after the meal. The insulinogenic index of all of these patients was below 43.2. The postprandial profiles were assessed at baseline and after 3 months of treatment with 50 mg/day sitagliptin after a meal (n = 11) or were untreated (control group; n = 10). This study was a prospective, open-label, non-blinded, non-randomized, clinical study.ResultsSitagliptin significantly decreased the plasma glucose levels at 60, 120, and 180 min, and significantly increased the plasma insulin levels at 0 and 30 min. There were no significant changes in glucose or insulin in the control group. The insulinogenic index increased significantly in the sitagliptin group compared with the control group (+16.7 vs. +0.1, P < 0.005). However, homeostasis model assessment of insulin resistance and the insulin sensitivity index were not significant different between the two groups.ConclusionAdministration of sitagliptin at 50 mg/day after a meal improved the impaired acute insulin response and suppressed postprandial hyperglycemia. Whereas the study is rather small and the design is suboptimal as it is not randomized and not blinded, these results suggest that sitagliptin is effective in Japanese patients with T2DM, many of whom display impaired acute insulin responses after a meal.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0071-1) contains supplementary material, which is available to authorized users.

Very Short-Term Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on the Secretion of Insulin, Glucagon, and Incretin Hormones in Japanese Patients with Type 2 Diabetes Mellitus: Analysis of Meal Tolerance Test Data

“…Therefore, the improvement in postprandial blood glucose shown in the present study may be more strongly associated with suppression of glucagon secretion than with enhancement of insulin secretion with sitagliptin treatment in the very short-term. This finding contrasts with the results of previous studies, which have shown that DPP-4 inhibitors, including sitagliptin, may improve acute insulin response in Japanese patients with type 2 diabetes by increasing early-phase insulin secretion [ 6 , 13 ]. The previous studies had a longer follow-up period (about 12 weeks), and therefore secondary effects, including glucose toxicity, could have contributed to the response.…”

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

“…However, some other researches conducted in non-diabetic subjects or type 2 diabetic subjects with a small sample size failed to observe any significant differences in insulin sensitivity between DPP4 inhibitor treatment group and placebo group [29,30]. Consistent with these data, we also found that increased DPP4 activities were positively associated with insulin resistance assessed by HOMA-IR in type 2 diabetic subjects.…”

Targeting beta-cell preservation in the management of type 2 diabetes

“…107,108 Treatment with either GLP-1 agonists or DPP-4 inhibitors, as monotherapy or in combination with other agents, can restore the first-phase insulin response. [109][110][111][112] In the Liraglutide and the Preservation of Pancreatic β-Cell Function in Early Type 2 Diabetes (LIBRA) trial, following elimination of glucotoxicity with four weeks of IIT, treatment with liraglutide for 48 weeks led to further improvement in baseline adjusted insulin secretion to OGTT in patients with T2D. 113 In animal studies, the protective effects of liraglutide on betacell function were more pronounced in the early stages of T2D than in the advanced stages.…”