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Aim This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin ( LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. Methods We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose ( FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. Results At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: −0.71%, 95% confidence interval: −1.04 to −0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at week 24 was −19.80 mg/ dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups. Conclusions This study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Aim: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus. Methods: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2-week single-blind placebo run-in, patients aged 18–75 years with a body mass index of 25–48 kg/m2 and baseline HbA1c of 7.3–11.0% were randomized 2:2:1 to receive once-daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD. Results: Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by −0.52% (p < 0.001) and −0.35% (p = 0.006), respectively (placebo-corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of −0.82, −0.64 and −0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo-corrected difference was −1.00 mmol/l (p < 0.001) for the 400 mg group and −0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC 0–2h in both the 400 and 200 mg groups (placebo corrected values −2.58 mmol/l/h, p < 0.001 and −1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin-treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12-week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively. Conclusions: Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose. [ABSTRACT FROM AUTHOR]