Of the 373 patients randomized in this trial, 186 and 187 patients were randomized to IDeg 200 U/mL and IDeg 100 U/mL, respectively. Two patients in the IDeg 200 U/mL group were withdrawn from the trial due to a randomization error before receiving the trial drug, and these patients were included in the FAS (n = 186) but not in the safety analysis set (n = 184; due to the lack of exposure to trial drug). A total of 166 (89%) and 172 (92%) patients completed the trial in the IDeg 200 and 100 U/mL groups, respectively.
The demographic and baseline characteristics were similar in the 2 treatment groups except for the proportion of females in either treatment group (52.7% and 37.4% of female patients in the IDeg 200 and 100 U/mL treatment groups, respectively). As shown in Table 1, study participants on average were 59.8 years of age, had a mean duration of T2DM of 12.8 years, a mean FPG of 149.6 mg/dL (8.3 mmol/L), and a mean BMI of 33.3 kg/m.
After 22 weeks of treatment, both IDeg 200 and 100 U/mL effectively improved glycemic control and reduced A1C to 7.3% and 7.5% by the end of the trial, respectively (Fig. 1 A). The estimated treatment difference (ETD, IDeg 200 U/mL – IDeg 100 U/mL) was −0.11% (95% CI −0.28 to 0.05), thus confirming the primary endpoint of noninferiority between the 2 treatment arms.
Glycemic control over time for (A) glycosylated hemoglobin A1C, (B) fasting plasma glucose, and (C) 9-point self-measured plasma glucose profile. OD, once daily
Observed mean FPG decreased by 41.4 mg/dL (2.3 mmol/L) with IDeg 200 U/mL and by 43.2 mg/dL (2.4 mmol/L) with IDeg 100 U/mL. The most notable change in FPG was observed during the first half of the treatment period (i.e., up to Week 10), and remained stable throughout the remainder of the trial period (Fig. 1 B). There was no statistically significant difference in the estimated mean between the 2 groups (IDeg 200 U/mL – IDeg 100 U/mL: 1.98 mg/dL, 95% CI −6.13 to 9.91; 0.11 mmol/L, 95% CI −0.34 to 0.55).
SMPG 9-point profiles demonstrated a reduction in FPG from baseline (Week 0) to the end of the trial (Week 22) in both treatment groups with no apparent differences (Fig. 1 C). By the end of the trial there was no statistically significant difference between the treatment groups.
Basal Insulin Dose and Body Weight
The baseline mean daily basal insulin doses were similar in both treatment groups (48 and 49 U for IDeg 200 and 100 U/mL, respectively). The mean daily basal insulin dose increased throughout the trial in both treatment groups to similar levels (77 and 76 U for IDeg 200 and 100 U/mL respectively) by the end of the trial. On average, 38% of subjects required >80 U/day and 6% required >160 U/day at the end of the trial, and these values were similar in both arms.
Mean body weight similarly increased in both treatment groups (2.0 kg) throughout the trial and the ETD (IDeg 200 U/mL – IDeg 100 U/mL) was −0.11 kg (95% CI −0.78 to 0.56) at the end of the trial, with no significant difference between the 2 treatment groups.
The proportion of patients with confirmed hypoglycemic episodes during the treatment period was similar in the IDeg 200 and 100 U/mL groups (55% and 52%, respectively) as was the observed rate of confirmed hypoglycemic episodes (5.17 and 5.66 events per patient-year of exposure [PYE], respectively). The estimated RR (IDeg 200 U/mL/IDeg 100 U/mL) was 0.96 (95% CI 0.67 to 1.36), and there was no statistically significant difference between the treatment groups (Table 2).
The observed rate of nocturnal confirmed hypoglycemic episodes was low in both treatment arms: 1.27 for IDeg 200 U/mL and 1.70 for IDeg 100 U/mL (Table 2). The RR (IDeg 200 U/mL/IDeg 100 U/mL) was 0.93 (95% CI 0.56 to 1.55), demonstrating that there was no statistically significant difference between the 2 treatment groups. There were 2 severe hypoglycemic episodes recorded during trial, 1 within each treatment group, neither of which occurred during the nocturnal period (Table 2). Due to the small number of events, statistical analyses could not be performed on the severe hypoglycemic episodes.
The proportion of subjects with AEs was similar in the IDeg 200 and 100 U/mL groups (61% and 59%, respectively) but the overall rate of AEs was numerically higher in the 200 U/mL compared to the 100 U/mL group (416 and 300 events per 100 PYE, respectively). The majority of AEs were mild or moderate and were considered by the investigator to be unrelated to either trial drug and had resolved by the end of the trial. The most frequently reported AEs (i.e., reported by ≥5% of patients) in the 2 treatment groups were nasopharyngitis, upper respiratory tract infection, and diarrhea, all of which occurred at a numerically higher rate in the IDeg 200 U/mL group (0.76 per PYE vs. 0.37 per PYE). The proportion of serious AEs was similar (5–6%) in both treatment groups, and 1 serious AE (hypoglycemia) was considered possibly or probably related to the trial drug (IDeg 100 U/mL). A total of 5 patients in the IDeg 200 U/mL and 2 patients in the IDeg 100 U/mL groups reported injection-site reactions throughout the trial period.