Effects of Once-daily Sitagliptin on 24-h Glucose Control Following 4 Weeks of Treatment in Japanese Patients with Type 2 Diabetes Mellitus

Abstract

The aim of the study was to assess the efficacy/safety of once- (100 mg q.d.) or twice-daily (50 mg b.i.d.) sitagliptin 100 mg/day in Japanese patients with type 2 diabetes (T2DM). In this randomized, double-blind study, 80 patients with inadequate glycemic control (HbA1c=6.5-10%; FPG </=15.0 mmol/l) were randomized equally to sitagliptin 100 mg q.d., 50 mg b.i.d. or placebo for 4 weeks. At baseline and Week 4, frequent blood sampling was performed to assess 24-h weighted mean glucose (24-h WMG). Patients in the efficacy analyses (n=76) had a mean baseline HbA1c of 7.7%. At Week 4, least-squares mean changes in 24-h WMG were reduced with sitagliptin 100 mg q.d. and 50 mg b.i.d. versus placebo (-1.9, -1.6, and -0.5 mmol/l, respectively; p<0.001). Sitagliptin significantly improved FPG and 2-h PPG compared to placebo. No significant differences in 24-h WMG, FPG, or 2-h PPG were observed between the sitagliptin groups. Sitagliptin was well tolerated with no hypoglycemic events. In Japanese patients with T2DM, sitagliptin 100 mg/day provided substantial and continuous 24-h glucose-lowering over 4 weeks. The same glucose-lowering efficacy and tolerability were observed with sitagliptin 100 mg/day whether administered as a once-daily or twice-daily regimen. These results support a once-daily dosing regimen in Japanese patients with T2DM.

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

“…[35][36][37][38][41][42][43][44][45]47,53 The low degree of Sitagliptin in the treatment of type 2 diabetes Dovepress submit your manuscript | www.dovepress.com Dovepress hypoglycemia is especially seen when compared with the risk of hypoglycemia during treatment with sulfonylurea ( Figure 4). This is explained by the glucose-dependency of the islet effects of GLP-1; hence when glucose levels are reduced the effects of GLP-1 in stimulating insulin secretion and inhibiting glucagon secretion vanish.…”

“…[36][37][38][39][40][41][42][43][44][45][46] Improved β-cell function is also evident from reduced proinsulin to insulin ratio. 38,[41][42][43][44]47 Sitagliptin also reduces glucagon levels, 25,30 although this needs to be examined in more detail. The improved islet function by sitagliptin results in reduction of both fasting glucose and prandial glucose as revealed in different studies in subjects with type 2 diabetes.…”

“…30,33,34 Active GIP and GLP-1 levels are increased by sitagliptin by approximately 2-to 3-fold after meal ingestion or oral glucose. 30,33,34 This results in increased insulin secretion as judged from increased insulinogenic index [35][36][37][38][39][40] and the homeostasis model of assessment of β-cell function (HOMA-β). [36][37][38][39][40][41][42][43][44][45][46] Improved β-cell function is also evident from reduced proinsulin to insulin ratio.…”

“…30,33,34 This results in increased insulin secretion as judged from increased insulinogenic index [35][36][37][38][39][40] and the homeostasis model of assessment of β-cell function (HOMA-β). [36][37][38][39][40][41][42][43][44][45][46] Improved β-cell function is also evident from reduced proinsulin to insulin ratio. 38,[41][42][43][44]47 Sitagliptin also reduces glucagon levels, 25,30 although this needs to be examined in more detail.…”

Sitagliptin counteracts seasonal fluctuation of glycemic control

“…In 2009, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was approved as the first incretin enhancer for use in Japan [4][5][6][7][8][9][10][11] . Although it has been suggested that seasonal fluctuations of hemoglobin A1c (HbA1c) are noted in patients with type 2 diabetes, no reports have been published concerning the efficacy of antidiabetic agents for such fluctuations.…”