A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes

Abstract

Abstract. The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m 2 , respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.

Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials

“…After screening titles and abstracts, we retrieved 343 reports for full text screening. A total of 62 RCTs, including 13 from journals 10 11 12 13 14 15 16 17 18 19 20 21 22 23 and 49 from the trial registry (available from https://clinicaltrials.gov ) were included in the final analysis. The details of the study selection flow are described in Fig.…”

Role of anagliptin, a dipeptidyl peptidase-4 inhibitor, in managing type 2 diabetes: A systematic review and meta-analysis

“…In this meta-analysis, which included 10 RCTs, subgroup analyses were conducted based on the nature of the control group, either ACG or PCG. One study included a placebo in the control group, [19] and the other had no drug in the control group [16] ; these 2 studies were analyzed in the PCG. Eight studies that included an oral AHA in the control group were analyzed in the ACG.…”

“…It is important to note that the meta-analysis included only 2 RCTs involving a small number of subjects (n = 99), which might be insufficient to compare the HbA1c-lowering effect of anagliptin versus placebo. Out of the 2 included studies, 1 demonstrated a significant HbA1c reduction (0.73% more) with anagliptin than placebo, [19] while the other did not show a significant difference. [16] The low baseline HbA1c (7.2% ± 0.5%) in the later study may account for the nonsignificant HbA1c-lowering effect of anagliptin over placebo.…”

Development of Long-Acting Dipeptidyl Peptidase-4 Inhibitors: Structural Evolution and Long-Acting Determinants

“…22 Vildagliptin was launched later than the nonpeptide sitagliptin, 23 which is a once-daily, noncovalent DPP-4 inhibitor approved by the FDA in 2006. Subsequently, with the exception of twice-daily anagliptin, 24 seven other oncedaily DPP-4 inhibitors have been launched in various countries (saxagliptin, 25 alogliptin, 26 linagliptin, 27 teneligliptin, 28 gemigliptin, 29 evogliptin, 30 and gosogliptin, 31 see Figure 1). In addition, novel long-acting DPP-4 inhibitors with less frequent dosing regimens have been developed; two once-weekly DPP-4 inhibitors, omarigliptin 32 and trelagliptin, 33 were launched in Japan in 2015 (Figure 1).…”