Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes

Diabetes Care. 2015 Mar;38(3):394-402. doi: 10.2337/dc14-2365. Epub 2015 Jan 29.

Abstract

Objective: To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes.

Research design and 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.

Trial registration: ClinicalTrials.gov NCT01422876.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / administration & dosage*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides / administration & dosage*
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Linagliptin
  • Male
  • Middle Aged
  • Purines / administration & dosage*
  • Quinazolines / administration & dosage*
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • Linagliptin
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT01422876