title: Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin.
abstract: OBJECTIVE
  This study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin.
  
  
  METHODS
  This was a double-blind trial in adults with HbA1c ≥8.0% and ≤12.0% (64-108 mmol/mol), randomized to saxagliptin (SAXA) (5 mg/day) plus dapagliflozin (DAPA) (10 mg/day; n = 179), or SAXA (5 mg/day) and placebo (n = 176), or DAPA (10 mg/day) and placebo (n = 179) on background metformin extended release (MET) ≥1,500 mg/day. Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET.
  
  
  RESULTS
  Patients had a mean baseline HbA1c of 8.9% (74 mmol/mol), diabetes duration of 7.6 years, and a BMI of 32 kg/m(2). At week 24, the adjusted mean change from the baseline HbA1c was -1.5% (-16.1 mmol/mol) with SAXA+DAPA+MET versus -0.9% (-9.6 mmol/mol) with SAXA+MET (difference -0.59% [-6.4 mmol/mol], P < 0.0001) and -1.2% (-13.1 mmol/mol) with DAPA+MET (difference -0.27% [3.0 mmol/mol], P < 0.02). The proportion of patients achieving HbA1c <7% (53 mmol/mol) was 41% with SAXA+DAPA+MET versus 18% with SAXA+MET and 22% with DAPA+MET. Urinary and genital infections occurred in ≤1% of patients receiving SAXA+DAPA+MET. Hypoglycemia was infrequent, with no episodes of major hypoglycemia.
  
  
  CONCLUSIONS
  In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin, greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone.
authors.affiliation: Dallas Diabetes and Endocrine Center, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
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: Pamela
authors.initials: P
authors.lastname: Zee
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: William
authors.initials: W
authors.lastname: Cook
authors.affiliation: AstraZeneca, Wilmington, DE.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
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*; 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 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D004151:Dipeptides; D005960:Glucosides; C529054:dapagliflozin; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane