Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in type 2 diabetes according to baseline glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor use: A post hoc analysis of ONWARDS 1–5

Aims
To assess the treatment effects of once-weekly insulin icodec (icodec) versus once-daily basal insulin comparators in individuals with type 2 diabetes (T2D) according to baseline glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use.

Materials and Methods
This post hoc analysis of the randomized ONWARDS 1–5 trials of individuals with T2D assessed treatment outcomes by trial according to baseline GLP-1RA and/or SGLT2i use.

Results
At screening, 21.3% (801/3765) and 36.9% (1388/3765) of participants in ONWARDS 1–5 were treated with a GLP-1RA or an SGLT2i, respectively. Baseline characteristics were broadly similar across treatment arms irrespective of GLP-1RA/SGLT2i use; GLP-1RA users had numerically higher body mass indices than non-users. Across trials, there were no statistically significant treatment interactions by GLP-1RA or SGLT2i subgroups with respect to: change in glycated haemoglobin (HbA1c) and body weight from baseline to end of treatment (except for body weight change by SGLT2i use in ONWARDS 5); weekly basal insulin dose during the last 2 weeks of treatment (except SGLT2i use in ONWARDS 5); and achievement of HbA1c less than 7% without clinically significant or severe hypoglycaemia. Irrespective of GLP-1RA/SGLT2i use, the rates of clinically significant or severe hypoglycaemia were less than one episode per patient-year of exposure across all trials except ONWARDS 4 (basal-bolus trial).

Conclusions
The efficacy and hypoglycaemia profile of icodec versus once-daily comparators was generally consistent across ONWARDS trials irrespective of background GLP-1RA and/or SGLT2i use.