In Study F, there were 10% of subjects in the TRESIBA and 6.8% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.

Study G: TRESIBA Administered at the Same Time each Day or Any Time each Day as an Add-on to One and up to Three of the Following Oral Agents: Metformin, Sulfonylurea or Glinides or Pioglitazone

The efficacy of TRESIBA was eva luated in a 26-week randomized, open-label, multicenter trial in 687 patients with type 2 diabetes mellitus inadequately controlled on basal insulin alone, oral antidiabetic agents (OADs) alone or both basal insulin and OAD. Patients were randomized to TRESIBA injected once-daily at the same time each day (with the main evening meal), to TRESIBA injected once daily at any time each day or to insulin glargine U-100 injected once-daily according to the approved labeling. The any time each day TRESIBA arm was designed to simulate a worst-case scenario injection schedule of alternating short and long, once daily, dosing intervals (i.e., alternating intervals of 8 to 40 hours between doses). TRESIBA in this arm was dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Up to three of the following oral antidiabetes agents (metformin, sulfonylureas, glinides or thiazolidinediones) were administered as background therapy in both treatment arms.

The mean age of the trial population was 56.4 years and mean duration of diabetes was 10.6 years. 53.9% were male. 66.7% were White, 2.5% Black or African American. 10.6% were Hispanic. 5.8% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 29.6 kg/m2.

At week 26, the difference in HbA1c reduction from baseline between TRESIBA at alternating times and insulin glargine U-100 was 0.04% with a 95% confidence interval of [-0.12%; 0.20%]. This comparison met the pre-specified non-inferiority margin (0.4%). See Table 11.

Table 11: Results at Week 26 in a Trial Comparing TRESIBA at same and alternating times to Insulin glargine U-100 in Patients with Type 2 Diabetes Mellitus on OAD(s)*

 TRESIBA
at the same time each day ± OAD(s)*
 TRESIBA
at alternating times ± OAD(s)*
 Insulin glargine U-100 ± OAD(s)*
 
N
 228
 229
 230
 
HbA1c (%)
 
Baseline
 8.4
 8.5
 8.4
 
End of trial
 7.3
 7.2
 7.1
 
Adjusted mean change from baseline**
 -1.03
 -1.17
 -1.21
 
Estimated treatment difference [95%CI]

TRESIBA alternating- Insulin glargine U-100
  0.04 [-0.12;0.20]
 
Estimated treatment difference TRESIBA alternating – TRESIBA same
 -0.13
 
Proportion Achieving HbA1c < 7% at Trial End
 40.8%
 38.9%
 43.9%
 
FPG (mg/dL)
 
Baseline
 158
 162
 163
 
End of trial
 105
 105
 112
 
Adjusted mean change from baseline
 -54.2
 -55.0
 -47.5
 
Daily insulin dose
 
Baseline mean
 21 U
 19 U
 19 U
 
Mean dose after 26 weeks
 45 U
 46 U
 44 U
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