Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin

Int J Clin Pract. 2013 Aug;67(8):759-67. doi: 10.1111/ijcp.12212. Epub 2013 Jun 24.

Abstract

Background: In four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients.

Methods: Data from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA(1c); reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA(1c) and rates of response without experiencing hypoglycaemia.

Results: Large glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA(1c) ≥ 1.0%, 31.7-50.3% vs. 10.3-20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA(1c) ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin.

Conclusions: Whether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA(1c) vs. comparator, with a low incidence of hypoglycaemia.

Trial registration: ClinicalTrials.gov NCT00121667 NCT00295633 NCT00313313 NCT00327015.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Area Under Curve
  • Controlled Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptides / therapeutic use*
  • Drug Therapy, Combination
  • Glyburide / therapeutic use
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / therapeutic use
  • Treatment Outcome

Substances

  • Dipeptides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Metformin
  • saxagliptin
  • Adamantane
  • Glyburide

Associated data

  • ClinicalTrials.gov/NCT00121667
  • ClinicalTrials.gov/NCT00295633
  • ClinicalTrials.gov/NCT00313313
  • ClinicalTrials.gov/NCT00327015