One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin

Diabetes Obes Metab. 2016 Nov;18(11):1128-1133. doi: 10.1111/dom.12741. Epub 2016 Aug 19.

Abstract

Aims: Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis.

Materials and methods: Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on.

Results: The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on.

Conclusions: Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia.

Keywords: DPP-4 inhibitor; SGLT-2 inhibitor; dapagliflozin; metformin; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adult
  • Aged
  • Benzhydryl Compounds / administration & dosage*
  • Benzhydryl Compounds / adverse effects
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dipeptides / administration & dosage*
  • Dipeptides / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination / adverse effects
  • Female
  • Glucosides / administration & dosage*
  • Glucosides / adverse effects
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Dipeptides
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • dapagliflozin
  • Metformin
  • saxagliptin
  • Adamantane