TRESIBA
®
(insulin degludec injection)
7
14.3 Type 2 Diabetes – Adult
Study 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 Adult Patients
The efficacy of TRESIBA
®
was evaluated 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% were male. 88.4% were White, 7.1% Black or African American. 17.2% were Hispanic.
9.6% of patients had eGFR<60 mL/min/1.73m
2
. The mean BMI was approximately 31.1 kg/m
2
.
At week 52, the difference in HbA
1c
reduction from baseline between TRESIBA
®
and insulin
glargine U-100 was 0.09% with a 95% confidence interval of [-0.04%; 0.22%] and met the
pre-specified non-inferiority margin (0.4%); See Table 9.
Table 9: Results at Week 52 in a Trial Comparing TRESIBA
®
to Insulin Glargine
U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
TRESIBA
®
+ OAD(s)*
Insulin glargine U-100
+ OAD(s)*
N
773
257
HbA
1c
(%)
Baseline
8.2
8.2
End of trial
7.1
7.0
Adjusted mean change from baseline**
-1.06
-1.15
Estimated treatment difference [95%CI]
TRESIBA
®
- Insulin glargine U-100
0.09 [-0.04;0.22]
Proportion Achieving HbA
1c
< 7% at Trial End
51.7%
54.1%
FPG (mg/dL)
Baseline
174
174
End of trial
106
115
Adjusted mean change from baseline
-68.0
-60.2
Daily insulin dose
Baseline mean (starting dose)
10 U
10 U
Mean dose after 52 weeks
56 U
58 U
*OAD: oral antidiabetic agent
**The change from baseline to end of treatment visit in HbA
1c
was analyzed using ANOVA with treatment, region,
sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA
1c
as covariates.
In Study D, there were 20.6% of subjects in the TRESIBA
®
and 22.2% Insulin glargine arms for whom data was
missing at the time of the HbA
1c
measurement.
Study E: TRESIBA
®
U-200 Administered at the Same Time Each Day as an Add-on to Metformin
with or without a DPP-4 Inhibitor in Insulin Naïve Adult Patients
The efficacy of TRESIBA
®
U-200 was evaluated in a 26-week randomized, open-label, multicenter
trial in 457 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one or
more oral antidiabetic agents (OADs) at baseline. Patients were randomized to TRESIBA
®
U-200
once-daily with the evening meal or insulin glargine U-100 once-daily according to the approved
labeling. Both treatment arms were receiving metformin alone (84%) or in combination with a
DPP-4 inhibitor (16%) as background therapy.
The mean age of the trial population was 57.5 years and mean duration of diabetes was 8.2 years.
53.2% were male. 78.3% were White, 13.8% Black or African American. 7.9% were Hispanic.
7.5% of patients had eGFR <60 mL/min/1.73m
2
. The mean BMI was approximately 32.4 kg/m
2
.
At week 26, the difference in HbA
1c
reduction from baseline between TRESIBA
®
U-200 and
insulin glargine U-100 was 0.04% with a 95% confidence interval of [-0.11%; 0.19%] and met
the pre-specified non-inferiority margin (0.4%). See Table 10.
Table 10: Results at Week 26 in a Trial Comparing TRESIBA
®
U-200 to Insulin
Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
TRESIBA
®
U-200 + Met
± DPP-4
Insulin glargine U-100
+ Met ± DPP-4
N
228
229
HbA
1c
(%)
Baseline
8.3
8.2
End of trial
7.0
6.9
Adjusted mean change from baseline**
-1.18
-1.22
Estimated treatment difference [95%CI]
TRESIBA
®
- Insulin glargine U-100
0.04 [-0.11;0.19]
Proportion Achieving HbA
1c
< 7% at Trial End
52.2%
55.9%
FPG (mg/dL)
Baseline
172
174
End of trial
106
113
Adjusted mean change from baseline
-71.1
-63.5
Daily insulin dose
Baseline mean
10 U
10 U
Mean dose after 26 weeks
59 U
62 U
*OAD: oral antidiabetic agent
**The change from baseline to end of treatment visit in HbA
1c
was analyzed using ANOVA with treatment, region,
sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA
1c
as covariates. In Study
E, there were 12.3% of subjects in the TRESIBA
®
and 12.7% Insulin glargine arms for whom data was missing at
the time of the HbA
1c
measurement.
Study F: TRESIBA
®
Administered at the Same Time Each Day in Insulin Naïve Adult Patients as
an Add-on to One or More of the Following Oral Agents: Metformin, Sulfonylurea, Glinides or
Alpha-Glucosidase Inhibitors
The efficacy of TRESIBA
®
was evaluated in a 26-week randomized, open-label, multicenter trial
in Asia in 435 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one
or more oral antidiabetic agents (OADs) at baseline. Patients were randomized to TRESIBA
®
once-daily in the evening or insulin glargine U-100 once-daily according to the approved
labeling. Pre-trial oral antidiabetes agents were continued as background therapy except for
DPP-4 inhibitors or thiazolidinediones in both treatment arms.
The mean age of the trial population was 58.6 years and mean duration of diabetes was 11.6 years.
53.6% were male. All patients were Asian. 10.9% of patients had eGFR<60 mL/min/1.73m
2
. The
mean BMI was approximately 25.0 kg/m
2
.
At week 26, the difference in HbA
1c
reduction from baseline between TRESIBA
®
and insulin
glargine U-100 was 0.11% with a 95% confidence interval of [-0.03%; 0.24%] and met the
pre-specified non-inferiority margin (0.4%). See Table 11.
Table 11: Results at Week 26 in a Trial Comparing TRESIBA
®
to Insulin Glargine
U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
TRESIBA
®
+ OAD(s)*
Insulin glargine U-100
+ OAD(s)*
N
289
146
HbA
1c
(%)
Baseline
8.4
8.5
End of trial
7.2
7.1
Adjusted mean change from baseline**
-1.42
-1.52
Estimated treatment difference [95%CI]
TRESIBA
®
- Insulin glargine U-100
0.11 [-0.03 ; 0.24]
Proportion Achieving HbA
1c
< 7% at Trial End
40.8%
48.6%
FPG (mg/dL)
Baseline
152
156
End of trial
100
102
Adjusted mean change from baseline
-54.6
-53.0
Daily insulin dose
Baseline mean (starting dose)
9 U
9 U
Mean dose after 26 weeks
19 U
24 U
*OAD: oral antidiabetic agent
**The change from baseline to end of treatment visit in HbA
1c
was analyzed using ANOVA with treatment, region,
sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA
1c
as covariates. 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 HbA
1c
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 in Adult Patients
The efficacy of TRESIBA
®
was evaluated 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/1.73m
2
. The mean BMI was approximately
29.6 kg/m
2
.
At week 26, the difference in HbA
1c
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 12.
