title: 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).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: MedStar Health Research Institute, Hyattsville, MD, USA.
authors.forename: V R
authors.initials: VR
authors.lastname: Aroda
authors.affiliation: AMCR Institute Inc., Escondido, CA, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Bailey
authors.affiliation: Department of Endocrinology, CHU Nantes, l'Institut du Thorax, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Cariou
authors.affiliation: WISDEM Centre, University Hospitals of Coventry and Warwickshire, Coventry, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Raskin
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Zacho
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: T H
authors.initials: TH
authors.lastname: Andersen
authors.affiliation: Scripps Whittier Diabetes Institute, San Diego, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Philis-Tsimikas
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D000069450:Liraglutide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069450:Liraglutide; D008687:Metformin; C571886:insulin degludec
keywords: GLP-1; glycaemic control; type 2 diabetes