Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin

Diabetes Care. 2015 Mar;38(3):384-93. doi: 10.2337/dc14-2364. Epub 2015 Jan 12.

Abstract

Objective: To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin.

Research design and methods: Subjects were randomized to a combination of empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 141), empagliflozin 10 mg (n = 140), or linagliptin 5 mg (n = 132) as add-on to metformin for 52 weeks. The primary end point was change from baseline in HbA1c at week 24.

Results: At week 24, reductions in HbA1c (mean baseline 7.90-8.02% [62.8-64.1 mmol/mol]) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin; adjusted mean (SE) changes from baseline were -1.19% (0.06) (-13.1 mmol/mol [0.7]) with empagliflozin 25 mg/linagliptin 5 mg, -1.08% (0.06) (-11.8 mmol/mol [0.7]) with empagliflozin 10 mg/linagliptin 5 mg, -0.62% (0.06) (-6.8 mmol/mol [0.7]) with empagliflozin 25 mg, -0.66% (0.06) (-7.2 mmol/mol [0.7]) with empagliflozin 10 mg, and -0.70% (0.06) (-7.6 mmol/mol [0.7]) with linagliptin 5 mg (P < 0.001 for all comparisons). In these groups, respectively, 61.8, 57.8, 32.6, 28.0, and 36.1% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) had HbA1c <7% (<53 mmol/mol) at week 24. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across treatment arms (68.6-73.0%), with no hypoglycemic AEs requiring assistance.

Conclusions: Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were 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*
  • Benzhydryl Compounds / adverse effects
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides / administration & dosage*
  • Glucosides / adverse effects
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Linagliptin
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Purines / administration & dosage*
  • Purines / adverse effects
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Treatment Outcome
  • Weight Loss / drug effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01422876