A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea

Diabetes Obes Metab. 2014 May;16(5):443-50. doi: 10.1111/dom.12234. Epub 2013 Dec 8.

Abstract

Aims: To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea.

Methods: In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight.

Results: A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272).

Conclusion: Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated.

Keywords: DPP-4 inhibitor; antidiabetic drug; clinical trial; glycaemic control; incretin therapy; type 2 diabetes.

Publication types

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

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adult
  • Australia / epidemiology
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight / drug effects
  • Canada / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptides / administration & dosage*
  • Dipeptides / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • India / epidemiology
  • Korea / epidemiology
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Sulfonylurea Compounds / administration & dosage*
  • Thailand / epidemiology
  • Treatment Outcome
  • United Kingdom

Substances

  • Blood Glucose
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Metformin
  • saxagliptin
  • Adamantane