Endpoints and statistical analyses
cognitive impairment, hypoglycaemia
HYPOGLYCAEMIC EPISODE, HYPOGLYCAEMIA
Statistical analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA). The significance level was set to 5%. No multiplicity adjustment was performed. Unless otherwise stated, the analyses included all randomised participants receiving ≥1 dose of the trial product. In the subgroup analysis to investigate the physiological response to hypoglycaemia, each participant only contributed to the analysis if a clinically relevant PG decline occurred and/or hypoglycaemic symptoms were present during the hypoglycaemia induction experiments. Thus, a participant was only included in the analysis for each dose level (double or triple) and insulin product if hypoglycaemia induction after that specific dose level/insulin product led to clinically significant hypoglycaemia (defined as minimum [nadir] PG <3.0 mmol/l) and/or hypoglycaemic symptoms as judged by the investigator.The primary endpoint was clinically significant hypoglycaemia (PGPGThe duration of decline of PG during hypoglycaemia induction was assessed by the endpoints time to decline from PGIn the subgroup analysis, concentrations of counterregulatory hormones at PGAEs and hypoglycaemic episodes (other than those induced) during the treatment periods were summarised. The end of each treatment period was defined as 7 days after the last icodec dose and 2 days after the last glargine U100 dose. Total participant-years of exposure for the treatment period was longer for icodec (4.8 years) than for glargine U100 (1.6 years). Hypoglycaemic episodes were classified as level 1 (PG <3.9 mmol/l and ≥3.0 mmol/l), level 2 (PG <3.0 mmol/l) and level 3 (severe cognitive impairment requiring assistance for recovery) [