title: Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes.
abstract: OBJECTIVE
  To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment.
  
  
  METHODS
  Patients receiving treatment with stable metformin (stratum A) (screening HbA1c level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA1c 7.5-10.5% [58-91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA1c level of <7% (53 mmol/mol).
  
  
  RESULTS
  Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA1c reduction than placebo (-0.82 vs. -0.10% [-9 vs. -1.1 mmol/mol], P < 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA1c level of <7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (∼1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%).
  
  
  CONCLUSIONS
  Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy.
authors.affiliation: Katholieke Universiteit Leuven, Leuven, Belgium chantal.mathieu@med.kuleuven.be.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Aurelian Emil
authors.initials: AE
authors.lastname: Ranetti
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Danshi
authors.initials: D
authors.lastname: Li
authors.affiliation: AstraZeneca, Molndal, Sweden.
authors.forename: Ella
authors.initials: E
authors.lastname: Ekholm
authors.affiliation: AstraZeneca, Gaithersburg, MD.
authors.forename: William
authors.initials: W
authors.lastname: Cook
authors.affiliation: MedImmune, Gaithersburg, MD.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: AstraZeneca, Gaithersburg, MD.
authors.forename: Hungta
authors.initials: H
authors.lastname: Chen
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D004151:Dipeptides; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane