Efficacy and safety of alogliptin in patients with type 2 diabetes mellitus: A multicentre randomized double-blind placebo-controlled Phase 3 study in mainland China, Taiwan, and Hong Kong

J Diabetes. 2017 Apr;9(4):386-395. doi: 10.1111/1753-0407.12425. Epub 2016 Aug 1.

Abstract

Background: This study determined the efficacy and safety of once-daily oral alogliptin in patients from mainland China, Taiwan, and Hong Kong with type 2 diabetes mellitus.

Methods: In this Phase 3 multicenter double-blind placebo-controlled 16-week trial, 506 patients were randomized to receive once-daily alogliptin 25 mg or placebo: 185 in the monotherapy group, 197 in the add-on to metformin group, and 124 in the add-on to pioglitazone group. The primary efficacy variable was the change from baseline (CFB) in HbA1c at Week 16; other efficacy measures included CFB to Week 16 in fasting plasma glucose (FPG), incidence of marked hyperglycemia (FPG ≥11.1 mmol/L), and the incidence of clinical HbA1c ≤6.5 % (48 mmol/mol) and ≤7.0 % (53 mmol/mol) at Week 16. Safety was assessed throughout the trial.

Results: Alogliptin monotherapy provided a significantly greater decrease in HbA1c from baseline to Week 16 compared with placebo (-0.58 %; 95 % confidence interval [CI] -0.78 %, -0.37 %; P < 0.001). As an add-on to metformin or pioglitazone, alogliptin also significantly decreased HbA1c compared with placebo (-0.69 % [95 % CI -0.87 %, -0.51 %; P < 0.001] and -0.52 % [95 % CI -0.75 %, -0.28 %; P < 0.001], respectively). In any treatment group versus placebo, alogliptin led to greater decreases in FPG (P ≤ 0.004) and a higher percentage of patients who achieved an HbA1c target of ≤6.5 % and ≤7.0 % (P ≤ 0.003). No weight gain was observed in any treatment group. A similar percentage of patients experienced drug-related, treatment-emergent adverse events in the alogliptin and placebo arms. Four and two patients in the alogliptin and placebo arms, respectively, experienced mild or moderate hypoglycemia.

Conclusions: Alogliptin 25 mg once daily reduced HbA1c and FPG and enhanced clinical response compared with placebo when used as monotherapy or as an add-on to metformin or pioglitazone. Therapy with alogliptin was well tolerated.

Keywords: 2型糖尿病; Asian; HbA1c; alogliptin; type 2 diabetes mellitus; 亚洲; 阿格列汀.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Asian People
  • Blood Glucose / metabolism
  • China
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / ethnology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fasting / blood
  • Female
  • Glycated Hemoglobin / metabolism
  • Hong Kong
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone
  • Piperidines / therapeutic use*
  • Taiwan
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Piperidines
  • Thiazolidinediones
  • Uracil
  • Metformin
  • alogliptin
  • Pioglitazone