title: Addition of or switch to insulin therapy in people treated with glucagon-like peptide-1 receptor agonists: A real-world study in 66 583 patients.
abstract: Real world outcomes of addition or switch to insulin therapy in type 2 diabetes (T2DM) patients on glucagon-like paptide-1 receptor agonist (GLP-1RA) with inadequately controlled hyperglycaemia, are not known.
  
  
  
  Patients with T2DM (n = 66 583) with a minimum of 6 months of GLP-1RA treatment and without previous insulin treatment were selected. Those who added insulin (n = 39 599) or switched to insulin after GLP-1RA cessation (n = 4706) were identified. Adjusted changes in glycated haemoglobin (HbA1c), weight, systolic blood pressure (SBP), and LDL cholesterol were estimated over 24 months follow-up.
  
  
  
  Among those who continued with GLP-1RA treatment without adding or switching to insulin, the highest adjusted mean HbA1c change was achieved within 6 months, with no further glycaemic benefits observed during 24 months of follow-up. Addition of insulin within 6 months of GLP-1RA initiation was associated with 18% higher odds of achieving HbA1c <7% at 24 months, compared with adding insulin later. At 24 months, those who added insulin reduced HbA1c significantly by 0.55%, while no glycaemic benefit was observed in those who switched to insulin. Irrespective of intensification with insulin, weight, SBP and LDL cholesterol were significantly reduced by 3 kg, 3 mm Hg, and 0.2 mmol/L, respectively, over 24 months.
  
  
  
  Significant delay in intensification of treatment by addition of insulin is observed in patients with T2DM inadequately controlled with GLP-1RA. Earlier addition of insulin is associated with better glycaemic control, while switching to insulin is not clinically beneficial during 2 years of treatment. Non-responding patients on GLP-1RA would benefit from adding insulin therapy, rather than switching to insulin.
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
authors.forename: Olga
authors.initials: O
authors.lastname: Montvida
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Kerenaftali
authors.initials: K
authors.lastname: Klein
authors.affiliation: Warwick Medical School, University of Warwick, and University Hospitals Coventry and Warwickshire, Coventry, UK.
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester, UK.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Paul
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001793:Blood Preservation; D001835:Body Weight; D008078:Cholesterol, LDL / Q000378:metabolism; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D057286:Electronic Health Records; D000077270:Exenatide; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D008078:Cholesterol, LDL; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
keywords: 
  GLP-1 analogue; insulin therapy; pharmaco-epidemiology; type 2 diabetes