Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes

Diabet Med. 2013 Dec;30(12):1472-6. doi: 10.1111/dme.12267. Epub 2013 Jul 19.

Abstract

Aims: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus.

Methods: Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA(1c) and percentages of patients achieving HbA(1c) < 53 mmol/mol (< 7.0%) were assessed in study 14.

Results: No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA(1c) decreased with saxagliptin but increased with placebo.

Conclusion: Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years.

Trial registration: ClinicalTrials.gov NCT00121641 NCT00121667.

Publication types

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

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Time Factors
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00121641
  • ClinicalTrials.gov/NCT00121667