The mean age of the trial population was 43.7 years and mean duration of diabetes was 18.5 years. 57.6% were male. 97.6% were White, 1.8% Black or African American. 3.4% were Hispanic. 7.4% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 26.7 kg/m2.

At week 26, the difference in HbA1c reduction from baseline between TRESIBA administered at alternating times and insulin glargine U-100 was 0.17% with a 95% confidence interval of [0.04%; 0.30%] and met the pre-specified non-inferiority margin (0.4%). See Table 7.

Table 7: Results at Week 26 in a Trial Comparing TRESIBA Dosed Once Daily at the Same and at Alternating Times Each Day to Insulin glargine U-100 in Patients with Type 1 Diabetes Mellitus receiving Insulin aspart at mealtimes

 TRESIBA at the same time each day + Insulin aspart
 TRESIBA at alternating times + Insulin aspart
 Insulin glargine U-100 + Insulin aspart
 
N
 165
 164
 164
 
HbA1c (%)
 
Baseline
 7.7
 7.7
 7.7
 
End of trial
 7.3
 7.3
 7.1
 
Adjusted mean change from baseline*
 -0.41
 -0.40
 -0.57
 
Estimated treatment difference [95%CI]

TRESIBA alternating - Insulin glargine U-100
  0.17 [0.04;0.30]
 
Proportion Achieving HbA1c < 7% at Trial End
 37.0%
 37.2%
 40.9%
 
FPG (mg/dL)
   
Baseline
 179
 173
 175
 
End of trial
 133
 149
 151
 
Adjusted mean change from baseline
 -41.8
 -24.7
 -23.9
 
Daily basal insulin dose
 
Baseline mean
 28 U
 29 U
 29 U
 
Mean dose at end of study
 32 U
 36 U
 35 U
 
Daily bolus insulin dose
 
Baseline mean
 29 U
 33 U
 32 U
 
Mean dose at end of study
 27 U
 30 U
 35 U
 
*The change from baseline to end of treatment visit in HbA1c was analysed using ANOVA with treatment, region, sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA1c as covariates.

In Study C, there were 15.8% and 15.9% of subjects in the TRESIBA (same time and alternating times respectively) and 7.9% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.

14.2 Type 2 Diabetes – AdultStudy D: TRESIBA Administered at the Same Time each Day as an Add-on to Metformin with or without a DPP-4 inhibitor in Insulin Naïve Patients

The efficacy of TRESIBA was eva luated in a 52-week randomized, open-label, multicenter trial that enrolled 1030 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agents (OADs). Patients were randomized to TRESIBA once-daily with the evening meal or insulin glargine U-100 once-daily according to the approved labeling. Metformin alone (82.5%) or in combination with a DPP-4 inhibitor (17.5%) was used as background therapy in both treatment arms.

The mean age of the trial population was 59.1 years and mean duration of diabetes was 9.2 years. 61.9% we