**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 G, there were 11.4% subjects for TRESIBA (both same time and alternating times) and 11.7% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.

Study H: TRESIBA Administered at the Same Time each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes

The efficacy of TRESIBA was eva luated in a 52-week randomized, open-label, multicenter trial in 992 patients with type 2 diabetes mellitus inadequately controlled on premix insulin, bolus insulin alone, basal insulin alone, oral antidiabetic agents (OADs) alone or any combination thereof. Patients were randomized to TRESIBA once-daily with the main evening meal or insulin glargine U-100 once-daily according to the approved labeling. Insulin aspart was administered before each meal in both treatment arms. Up to two of the following oral antidiabetes agents (metformin or pioglitazone) were used as background therapy in both treatment arms.

The mean age of the trial population was 58.9 years and mean duration of diabetes was 13.5 years. 54.2% were male. 82.9% were White, 9.5% Black or African American. 12.0% were Hispanic. 12.4% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 32.2 kg/m2.

At week 52, the difference in HbA1c reduction from baseline between TRESIBA and insulin glargine U-100 was 0.08% with a 95% confidence interval of [-0.05%; 0.21%] and met the pre-specified non-inferiority margin (0.4%). See Table 12.

Table 12: Results at Week 52 in a Trial Comparing TRESIBA to Insulin glargine U-100 in Patients with Type 2 Diabetes Mellitus receiving Insulin aspart at mealtimes and OADs*

 TRESIBA + Insulin aspart ± OAD(s)*
 Insulin glargine U-100 + Insulin aspart ± OAD(s)*
 
N
 744
 248
 
HbA1c (%)
 
Baseline
 8.3
 8.4
 
End of trial
 7.1
 7.1
 
Adjusted mean change from baseline**
 -1.10
 -1.18
 
Estimated treatment difference [95%CI]

TRESIBA - Insulin glargine U-100
 0.08 [-0.05;0.21]
 
Proportion Achieving HbA1c < 7% at Trial End
 49.5%
 50.0%
 
FPG (mg/dL)
 
Baseline
 166
 166
 
End of trial
 122
 127
 
Adjusted mean change from baseline
 -40.6
 -35.3
 
Daily basal insulin dose
 
Baseline mean
 42 U
 41 U
 
Mean dose after 52 weeks
 74 U
 67 U
 
Daily bolus insulin dose
 
Baseline mean
 33 U
 33 U
 
Mean dose after 52 weeks
 70 U
 73 U
 
*OAD: oral antidiabetic agent

**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 H, there were 16.1% of subjects in the TRESIBA and 14.5% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.

Study I: TRESIBA Administered at Any Time each Day as an