Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study

Abstract

Summary Aims: To evaluate the efficacy and safety of alogliptin, a new dipeptidyl peptidase‐4 inhibitor, for 26 weeks at once‐daily doses of 12.5 and 25 mg in combination with metformin in patients whose HbA1c levels were inadequately controlled on metformin alone. Methods and patients: Patients with type 2 diabetes and inadequate glycaemic control (HbA1c 7.0‐10.0%) were randomised to continue a stable daily metformin dose regimen (≥ 1500 mg) plus the addition of placebo (n = 104) or alogliptin at once‐daily doses of 12.5 (n = 213) or 25 mg (n = 210). HbA1c, insulin, proinsulin, C‐peptide and fasting plasma glucose (FPG) concentrations were determined over a period of 26 weeks. Results: Alogliptin at either dose produced least squares mean (SE) decreases from baseline in HbA1c of −0.6 (0.1)% and in FPG of −17.0 (2.5) mg/dl [−1.0 (0.1) mmol/l], decreases that were significantly (p < 0.001) greater than those observed with placebo. The between treatment differences (alogliptin – placebo) in FPG reached statistical significance (p < 0.001) as early as week 1 and persisted for the duration of the study. Overall, adverse events (AEs) observed with alogliptin were not substantially different from those observed with placebo. This includes low event rates for gastrointestinal side effects and hypoglycaemic episodes. There was no dose‐related pattern of AE reporting between alogliptin groups and few serious AEs were reported. Conclusion: Alogliptin is an effective and safe treatment for type 2 diabetes when added to metformin for patients not sufficiently controlled on metformin monotherapy.

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

“…54 The effect of sitagliptin seems to be similar to other DPP-4 inhibitors, although head-to-headstudies have not been undertaken. 41,44,46,47,[58][59][60][61][62][63][64][65][66][67][68][69] Figure 4 shows the reduction in HbA 1c during 24-to 26-week studies with four different DPP-4 inhibitors as monotherapy or in combination with metformin, a sulfonylurea or a thiazolidinedione. Initial HbA 1c levels differed in the different studies; overall no clear difference between the various DPP-4 inhibitors is evident.…”

Application of pharmacometric approaches to evaluate effect of weight and renal function on pharmacokinetics of alogliptin

“…Patients were randomly assigned to one of four treatments: alogliptin at 25, 100 or 400 mg daily or placebo. The study consisted of a screening (day À7) visit, a baseline (day À1) period, a treatment (days 1-14) period and a follow-up (days [15][16][17][18][19][20][21] period [14].…”

“…Alogliptin exhibited various benefits including low risk of hypoglycaemia, a neutral effect on body weight and the potential for preservation or enhancement of β-cell function. Studies conducted with alogliptin in combination with antidiabetic agents provided significantly better glycaemic control than monotherapy with any of these agents alone [15][16][17][18][19][20][21].…”

Personalized genotyping!based therapy

“…В работе M.A. Nauck et al (2008) показано, что при СД2 в слу чае резистентности к препарату 1 й линии -мет формину при назначении алоглиптина улучшается гликемический профиль [12]. Основная гипотеза эффективного действия ингибиторов дипептидил пептидазы 4 исходит из того, что при назначении происходит деградация глюкагонподобного пепти да 1 и глюкозозависимого инсулинотропного пеп тида; с их помощью стимулируется пролиферация β клеток и ингибируется процесс их апоптоза.…”