title: Empagliflozin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Linagliptin and Metformin: A 24-Week Randomized, Double-Blind, Parallel-Group Trial.
abstract: To evaluate the efficacy and safety of empagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with linagliptin and metformin.
  
  
  
  Patients with HbA1c≥8.0% and ≤10.5% (≥64 and ≤91 mmol/mol) while receiving stable-dose metformin received open-label linagliptin 5 mg (n = 606) for 16 weeks. Subsequently, those with HbA1c≥7.0 and ≤10.5% (≥53 and ≤91 mmol/mol) were randomized to receive double-blind, double-dummy treatment with empagliflozin 10 mg (n = 112), empagliflozin 25 mg (n = 111), or placebo (n = 110) for 24 weeks; all patients continued treatment with metformin and linagliptin 5 mg. The primary end point was the change from baseline in HbA1cafter 24 weeks of double-blind treatment.
  
  
  
  At week 24, empagliflozin significantly reduced HbA1c(mean baseline 7.96-7.97% [63-64 mmol/mol]) versus placebo; the adjusted mean differences in the change from baseline with empagliflozin 10 and 25 mg versus placebo were -0.79% (95% CI ‒1.02, ‒0.55) (-8.63 mmol/mol [‒11.20, ‒6.07 mmol/mol]) and -0.70% (95% CI ‒0.93, ‒0.46) (-7.61 mmol/mol [‒10.18, ‒5.05 mmol/mol]), respectively (both P < 0.001). Fasting plasma glucose and weight were significantly reduced in both empagliflozin groups versus placebo (P < 0.001 for all comparisons). More patients receiving placebo than empagliflozin 10 and 25 mg reported adverse events during double-blind treatment (68.2%, 55.4%, and 51.8%, respectively).
  
  
  
  Empagliflozin treatment for 24 weeks improved glycemic control and weight versus placebo as an add-on to linagliptin 5 mg and metformin and was well tolerated.
authors.affiliation: Haukeland University Hospital, Bergen, Norway eirik.softeland.med@helse-bergen.no.
authors.forename: Eirik
authors.initials: E
authors.lastname: Søfteland
authors.affiliation: Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Boehringer Ingelheim Norway KS, Asker, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Vangen
authors.affiliation: Boehringer Ingelheim Ltd., Bracknell, Berkshire, U.K.
authors.forename: Robert
authors.initials: R
authors.lastname: Toorawa
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Maldonado-Lutomirsky
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; C570240:empagliflozin