title: Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: the EASIE post-hoc analysis and extension trial.
abstract: OBJECTIVE
  We examined the effects of adding glargine to metformin-sitagliptin (MS+G) or sitagliptin to metformin-glargine (MG+S) therapy in type 2 diabetic persons uncontrolled after 24-week MS or MG dual therapy.
  
  
  METHODS
  Subjects with A1c≥7% on MS or MG treatment were respectively given glargine (0.2U/kg starting dose) or sitagliptin (100mg daily) for 12weeks. The primary endpoint was number of subjects attaining A1c goal defined as <7%.
  
  
  RESULTS
  After receiving 24-week MS or MG dual therapy in the original EASIE Study, 42% (104/248) on MS and 68% (152/224) on MG attained A1c<7% (p<0.0001). The reduction in A1c was negatively associated with baseline fasting blood glucose (FBG) only in the MG group. Reduction in A1c was not related to baseline postprandial blood glucose (PPBG) in either the MG or MS group. Amongst 194 eligible patients, 57.7% (n=111) entered the 12-week extension trial [MS+G:74/131, 57.3%; MG+S:37/63, 58.7%) with 55 (51.9%) subjects attaining goal [MS+G:59.2%; MG+S:37.1%] at week 12. The final insulin dosage was similar in both groups [MS+G: 0.46U/kg; MG+S: 0.45U/kg] with a higher rate of hypoglycemia in the MG+S (6.5 events/patient-year) than the MS+G group (3.2 events/patient-year), although neither group had severe hypoglycemia.
  
  
  CONCLUSIONS
  In metformin-treated type 2 diabetes patients, high fasting BG predicted greater A1c reductions with the addition of glargine, but not with sitagliptin. In subjects uncontrolled with 6-month dual therapy of MS or MG, 50% attained A1c<7% with triple therapy of MS+G or MG+S in 12weeks. The increased rate of hypoglycemia with MG+S (but not with MS+G) underlines the need to take measures to avoid the hypoglycemia.
authors.affiliation: Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. Electronic address: jchan@cuhk.edu.hk.
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.affiliation: Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia.
authors.forename: Pablo
authors.initials: P
authors.lastname: Aschner
authors.affiliation: Diabetes Research Group, Institute of Life Science, Swansea University, Swansea, Wales, United Kingdom.
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
authors.affiliation: Point Medical Rond Point de la Nation, Dijon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Picard
authors.affiliation: Sanofi, Paris, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Vincent
authors.affiliation: Sanofi, Paris, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Dain
authors.affiliation: Sanofi, Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Pilorget
authors.affiliation: Lincoln, Chilly-Mazarin, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Loizeau
authors.affiliation: Rafic Hariri University Hospital, Beirut, Lebanon.
authors.forename: Akram
authors.initials: A
authors.lastname: Echtay
authors.affiliation: Tulane University Medical Center, New Orleans, LA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D000069036:Insulin Glargine / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D000069036:Insulin Glargine; D008687:Metformin; D000068900:Sitagliptin Phosphate
keywords: A1c; EASIE; Insulin glargine; Metformin; Sitagliptin; Type 2 diabetes