Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial

Diabetes Care. 2018 May;41(5):1009-1016. doi: 10.2337/dc17-1114. Epub 2018 Feb 26.

Abstract

Objective: In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin.

Research design and methods: A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin glargine (IGlar U100) 20-50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day.

Results: Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] -0.02% [95% CI -0.16, 0.12]; -0.2 mmol/mol [95% CI -1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose-confirmed symptomatic hypoglycemia events was lower with IDegLira versus basal-bolus (risk ratio 0.39 [95% CI 0.29, 0.51]; rate ratio 0.11 [95% CI 0.08, 0.17]). Body weight decreased with IDegLira and increased with basal-bolus (ETD -3.6 kg [95% CI -4.2, -2.9]). Fasting plasma glucose reductions were similar; lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower with basal-bolus. Sixty-six percent of patients on IDegLira vs. 67.0% on basal-bolus achieved HbA1c <7.0% (53 mmol/mol). Total daily insulin dose was lower with IDegLira (40 units) than basal-bolus (84 units total; 52 units basal).

Conclusions: In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA1c reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.

Trial registration: ClinicalTrials.gov NCT02420262.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects*
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin Aspart / administration & dosage
  • Insulin Aspart / adverse effects
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / adverse effects
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / adverse effects*
  • Liraglutide / administration & dosage*
  • Liraglutide / adverse effects*
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Treatment Outcome

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • IDegLira
  • Insulin
  • Insulin, Long-Acting
  • insulin degludec, insulin aspart drug combination
  • Insulin Glargine
  • Liraglutide
  • Metformin
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT02420262