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

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.

Author information

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.
Warwick Medical School, University of Warwick, and University Hospitals Coventry and Warwickshire, Coventry, UK.
Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester, UK.



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.


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

[Indexed for MEDLINE]

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