Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus: a 2-year study

Diabetes Obes Metab. 2014 Dec;16(12):1239-46. doi: 10.1111/dom.12377. Epub 2014 Sep 25.

Abstract

Aims: To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin.

Methods: This multicentre, double-blind, active-controlled study randomized 2639 patients aged 18-80 years to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once daily (n = 880), alogliptin 25 mg once daily (n = 885) or glipizide 5 mg once daily, titrated to a maximum of 20 mg (n = 874). The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks.

Results: The mean patient age was 55.4 years, the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6%. HbA1c reductions at week 104 were -0.68%, -0.72% and -0.59% for alogliptin 12.5 and 25 mg and glipizide, respectively [both doses met the criteria for non-inferiority to glipizide (p<0.001); alogliptin 25 mg met superiority criteria (p=0.010)]. Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg, respectively, and increased by 0.30 mmol/l for glipizide (p < 0.001 for both comparisons with glipizide). Mean weight changes were -0.68, -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide, respectively (p < 0.001 for both comparisons with glipizide). Hypoglycaemia occurred in 23.2% of patients in the glipizide group vs. 2.5 and 1.4% of patients in the alogliptin 12.5 and 25 mg groups, respectively. Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group.

Conclusions: Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone.

Keywords: DPP-IV inhibitor; antidiabetic drug; diabetes mellitus; glycaemic control; incretin therapy; randomised trial.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / chemically induced
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glipizide / administration & dosage
  • Glipizide / adverse effects
  • Glipizide / therapeutic use*
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Pancreatitis / chemically induced
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Treatment Outcome
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Piperidines
  • hemoglobin A1c protein, human
  • Uracil
  • Metformin
  • alogliptin
  • Glipizide