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

Diabetes Obes Metab. 2017 Jan;19(1):108-117. doi: 10.1111/dom.12790. Epub 2016 Oct 18.


Background: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: GLP-1 analogue; insulin therapy; pharmaco-epidemiology; type 2 diabetes.

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Blood Preservation
  • Body Weight
  • Cholesterol, LDL / metabolism
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Substitution
  • Drug Therapy, Combination
  • Electronic Health Records
  • Exenatide
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Peptides / therapeutic use*
  • Treatment Outcome
  • Venoms / therapeutic use*


  • Blood Glucose
  • Cholesterol, LDL
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Venoms
  • hemoglobin A1c protein, human
  • Liraglutide
  • Exenatide