Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial

Diabetes Obes Metab. 2017 Jun;19(6):858-865. doi: 10.1111/dom.12892. Epub 2017 Mar 3.

Abstract

Aims: To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes.

Research design and methods: This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210).

Results: Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI , 1.30 mmol/mol [-0.41; 3.01]95%CI ). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was -1.0 kg vs -2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively.

Conclusion: A pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naïve patients.

Trial registration: ClinicalTrials.gov NCT02298192.

Keywords: efficacy; insulin therapy; randomized clinical trials; safety; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Algorithms
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Equivalence Trials as Topic
  • Female
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin, Long-Acting / administration & dosage*
  • Liraglutide / administration & dosage*
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / administration & dosage*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • IDegLira
  • Insulin, Long-Acting
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Liraglutide
  • Metformin
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT02298192