title: Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study.
abstract: OBJECTIVE
  The PROMPT study compared efficacy and tolerability of two treatment intensification strategies: adding saxagliptin or uptitrating metformin monotherapy, in patients with type 2 diabetes (T2D) and inadequate glycaemic control on a sub-maximal metformin dose.
  
  
  METHODS
  In this double-blind, 24-week study, metformin-tolerant patients with T2D on metformin monotherapy were randomised to receive fixed-dose metformin 1500 mg/day, plus either add-on saxagliptin 5 mg/day (SAXA-MET) or a two-step metformin uptitration (MET-UP) to a maximum dose (2500 mg/day).
  
  
  BACKGROUND
  NCT01006590.
  
  
  METHODS
  Primary: absolute change from baseline in glycated haemoglobin A(1c) (HbA(1c)) (Week 24). Secondary: proportion of patients achieving a therapeutic glycaemic response (Week 24); change from baseline in fasting plasma glucose (Week 24); safety and tolerability. Exploratory analyses comprised three patient-related questionnaires, including the validated 5-dimension Digestive Health Status Index (DHSI).
  
  
  RESULTS
  A total of 286 patients were randomised: (SAXA-MET: 147; MET-UP: 139). Baseline mean (SD) HbA(1c): 7.71 (0.85; SAXA-MET); 7.80 (0.82; MET-UP). Adjusted mean reductions from baseline in HbA(1c) (Week 24): -0.47% (SAXA-MET); -0.38% (MET-UP); mean (95% CI) difference in treatment effect, -0.10% (-0.26, 0.07); p = 0.260. The proportion of patients (95% CI) achieving a therapeutic glycaemic response (HbA(1c) < 7%): 43.8% (34.8, 49.6) (SAXA-MET) vs. 35.0% (29.0, 43.8) (MET-UP). Of the five DHSI domains, mean (95% CI) differences were observed for diarrhoea-predominant score (+0.8 [-2.5, 4.0] vs. +7.9 [4.6, 11.2]) and dysmotility score (-0.5 [-2.0, 1.0] vs. +1.9 [0.3, 3.4]), (SAXA-MET and MET-UP, respectively). The most common adverse event was diarrhoea: 6.1% (SAXA-MET) vs. 12.2% (MET-UP).
  
  
  CONCLUSIONS
  In metformin-tolerant patients with T2D (inadequately controlled on sub-maximal metformin monotherapy), saxagliptin was well tolerated. Although HbA(1c) reduction was not significantly different between treatment groups, the lower occurrence of gastrointestinal symptoms in the SAXA-MET group suggests that saxagliptin add-on treatment may be a suitable alternative treatment strategy to metformin uptitration.
authors.affiliation: Endocrinologie et Nutrition, Cliniques universitaires Saint-Luc, Brussels, Belgium. michel.hermans@diab.ucl.ac.be
authors.forename: Michel P
authors.initials: MP
authors.lastname: Hermans
authors.forename: Tuncay
authors.initials: T
authors.lastname: Delibasi
authors.forename: Ian
authors.initials: I
authors.lastname: Farmer
authors.forename: Leif
authors.initials: L
authors.lastname: Lohm
authors.forename: Pierre
authors.initials: P
authors.lastname: Maheux
authors.forename: PierMarco
authors.initials: P
authors.lastname: Piatti
authors.forename: Elmas
authors.initials: E
authors.lastname: Malvolti
authors.forename: Silke
authors.initials: S
authors.lastname: Jörgens
authors.forename: Bernard
authors.initials: B
authors.lastname: Charbonnel
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane