Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data

Diabetes Obes Metab. 2015 Jun;17(6):581-590. doi: 10.1111/dom.12459. Epub 2015 Apr 6.

Abstract

Aims: To assess the long-term efficacy and tolerability of dapagliflozin versus glipizide as add-on to metformin in patients with inadequately controlled type 2 diabetes.

Methods: The present study was an extension of an earlier randomized, double-blind, phase III study of dapagliflozin (n = 406) vs glipizide (n = 408) to 208 weeks (4 years). Patients continued to receive their assigned medication. No statistical treatment-group comparisons were calculated.

Results: At 208 weeks, dapagliflozin compared with glipizide produced sustained reductions in glycated haemoglogin (HbA1c): -0.30% [95% confidence interval (CI), -0.51 to -0.09], in total body weight: -4.38 kg (95% CI -5.31 to -3.46) and in systolic blood pressure (SBP): -3.67 mmHg (95% CI -5.92 to -1.41). The HbA1c coefficient of failure was significantly lower for dapagliflozin than for glipizide: 0.19 (95% CI 0.12-0.25) versus 0.61 (95% CI 0.49-0.72, difference -0.42; p = 0.0001). Dapagliflozin was not associated with glomerular function deterioration, while this occurred more frequently in patients in the glipizide group. Fewer patients reported hypoglycaemia in the dapagliflozin compared with the glipizide group (5.4 vs 51.5%). Genital and urinary tract infections were more common with dapagliflozin than with glipizide, but their incidence decreased with time and all events responded well to antimicrobial treatment.

Conclusions: In patients completing 4 years of treatment, dapagliflozin was well tolerated and associated with sustained glycaemic efficacy and greater reductions in body weight and SBP versus glipizide.

Keywords: SGLT2 inhibitor; dapagliflozin; durability; efficacy; safety; type 2 diabetes.

Publication types

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

MeSH terms

  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination / methods
  • Female
  • Glipizide / therapeutic use*
  • Glomerular Filtration Rate / drug effects
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Treatment Outcome
  • Urinary Tract Infections / chemically induced

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • dapagliflozin
  • Metformin
  • Glipizide