title: Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes.
  
  
  METHODS
  Subjects not receiving antidiabetes therapy for ≥12 weeks were randomized to empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 135), empagliflozin 10 mg (n = 134), or linagliptin 5 mg (n = 135) for 52 weeks. The primary end point was change from baseline in HbA1c at week 24.
  
  
  RESULTS
  Mean HbA1c at baseline was 7.99-8.05% (64 mmol/mol). At week 24, adjusted mean (SE) changes from baseline in HbA1c with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg were -1.08 (0.06)% (-11.8 [0.7] mmol/mol), -1.24 (0.06)% (-13.6 [0.7] mmol/mol), -0.95 (0.06)% (-10.4 [0.7] mmol/mol), -0.83 (0.06)% (-9.1 [0.7] mmol/mol), and -0.67 (0.06)% (-7.3 [0.7] mmol/mol), respectively. Reductions in HbA1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg (P < 0.001) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components (P < 0.001 for both). At week 24, 55.4%, 62.3%, 41.5%, 38.8%, and 32.3% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) reached HbA1c <7% with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg, respectively. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across groups (68.9-81.5%), with no confirmed hypoglycemic AEs.
  
  
  CONCLUSIONS
  Reductions from baseline in HbA1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg. Empagliflozin/linagliptin was well tolerated.
authors: National Research Institute, Los Angeles, CA.
authors: Andrew
authors: A
authors: Lewin
authors: University of Texas Health Science Center, San Antonio, TX defronzo@uthscsa.edu.
authors: Ralph A
authors: RA
authors: DeFronzo
authors: Boehringer Ingelheim Ltd., Bracknell, Berkshire, U.K.
authors: Sanjay
authors: S
authors: Patel
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT.
authors: Dacheng
authors: D
authors: Liu
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT.
authors: Renee
authors: R
authors: Kaste
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors: Hans J
authors: HJ
authors: Woerle
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors: Uli C
authors: UC
authors: Broedl
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D011687:Purines; D011799:Quinazolines; C570240:empagliflozin