Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study)

Diabetes Obes Metab. 2016 Jul;18(7):663-70. doi: 10.1111/dom.12661. Epub 2016 May 2.

Abstract

Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control.

Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (≥1500 mg) were randomized to addition of once-daily IDeg ('IDeg add-on to liraglutide' arm; n = 174) or placebo ('placebo add-on to liraglutide' arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines.

Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (-1.04%) than in the placebo add-on to liraglutide arm (-0.16%; p < 0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p < 0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ∼3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and -1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach.

Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.

Trial registration: ClinicalTrials.gov NCT01664247.

Keywords: GLP-1; glycaemic control; type 2 diabetes.

Publication types

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

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fasting / blood
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / 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
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • insulin degludec
  • Liraglutide
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT01664247