Diabetes Research and Clinical Practice - Volume 106 - Supplement 1 - November 2014 - page 11

S4
Oral presentation abstracts / Diabetes Research and Clinical Practice 106S1 (2014) S1–S41
fed serum triglyceride. CNX-013-B2 increases non-statistical
significant fed insulin levels and improves muscle insulin
sensitivity without increase in body weight. There was no
change in the relative or absolute weight of liver, kidney,
heart, and the different adipose depots. CNX-013-B2 shown
non-significant decrease in heart triglyceride levels, increased
phospho-AMPK levels, inhibited p70S6K pathway (reduces
phospho-mTOR levels) and thus regulate protein synthesis.
CNX-013-B2 reduces JNK signaling in heart significantly and
enhances fat oxidation.
Conclusion:
These findings indicate that CNX-013-B2, an
orally bio available selective rexinoid has a potential to
provide good glycemic control and reduce cardiac hypertrophy
and can be good therapeutic agent for the treatment of type 2
diabetes.
OP7
EFFICACY, SAFETY, AND TOLERABILITY OF IPRAGLIFLOZIN
IN ASIAN TYPE 2 DIABETIC PATIENTS WITH INADEQUATE
GLYCEMIC CONTROL WITH METFORMIN. RESULTS
OF A PHASE 3 RANDOMIZED, PLACEBO-CONTROLLED,
DOUBLE-BLIND, MULTICENTER TRIAL
L.-M. Chuang
1
, K.W. Min
2
, C.-H. Lu
3
, S. Kokubo
4
, S. Yoshida
4
,
B.S. Cha
5
.
1
National Taiwan University Hospital, Taipei, Taiwan;
2
Eulji General Hospital, Seoul, Korea, Republic of ;
3
Chiayi Christian
Hospital, Chiayi City, Taiwan;
4
Astellas Pharma Inc., Tokyo, Japan;
5
Yonsei University College of Medicine, Seoul, Korea, Republic of
Background:
Ipragliflozin, a sodium-glucose cotransporter 2
(SGLT2) inhibitor, was recently approved in Japan for the
treatment of type 2 diabetes. The objective of the present
study was to examine the efficacy and safety of ipragliflozin
in combination with metformin in Asian patients with type 2
diabetes in Taiwan and Korea.
Method:
In this phase 3, multicenter, placebo-controlled,
double-blind, parallel-group study, patients at 18 sites in
Korea and 12 sites in Taiwan were randomized to either
50mg ipragliflozin or placebo for 24 weeks while continuing
metformin. All patients entered a 2-week run-in period
before randomization. The main inclusion criteria were:
age 20 years, diagnosis of type 2 diabetes 12 weeks
before enrollment, stable diet and exercise regimen for 8
weeks, hemoglobin A1c (HbA1c) of 7.0–10.0%, body mass
index of 20.0–45.0 kg/m
2
, and on a stable metformin dose of
1500mg/day (or 1000mg/day if safety concerns prohibited
higher doses) for 8 weeks. Patients using other oral agents
entered an 8-week washout before the run-in period. Efficacy
outcomes included the changes in HbA1c (primary efficacy
outcome), fasting plasma glucose (FPG), fasting serum insulin,
body weight (BW), waist circumference (WC) from baseline
to the end of treatment (EOT) (with last observation carried
forward [secondary efficacy outcomes]), and the proportion of
patients with HbA1c
<
7.0% and
<
6.5% at EOT. Safety outcomes
included treatment-emergent adverse events (TEAEs).
Result:
Between November 2011 and January 2013, 171
patients were randomized to and administered ipragliflozin
(
N
= 87) or placebo (
N
= 83). The mean changes (± standard
deviation) in HbA1c were significantly greater [−0.94±0.75%
(baseline: 7.74±0.78%)] in the ipragliflozin group than in
the placebo group [−0.47±0.81% (baseline: 7.75±0.72%)] with
placebo-adjusted mean difference of −0.47% (P
<
0.001). The
proportions of patients with HbA1c
<
6.5% in the ipragliflozin
and placebo groups increased from 1.1% (1/87) and 0%
(0/83), respectively, at baseline to 25.9%, (22/85) and 9.6%
(8/83), respectively, at EOT. The proportions of patients with
HbA1c
<
7.0% in the ipragliflozin and placebo groups increased
from 11.5% (10/87) and 3.6% (3/83), respectively, at baseline
to 69.4% (59/85) and 44.6% (37/83), respectively, at EOT.
The changes in FPG, BW and WC were also significantly
greater in the ipragliflozin group than in the placebo group,
with placebo-adjusted mean differences of −14.1mg/dL,
−1.24 kg, and −0.91 cm, respectively (P
<
0.001 for FPG and BW,
P = 0.032 for WC). The reductions in systolic blood pressure
(−6.8±14.1 vs. −1.3±12.9mmHg), diastolic blood pressure
(−3.7±9.4 vs. −1.0±8.0mmHg) and triglycerides (−24.6±91.9 vs.
+10.7±79.6mg/dL) were greater in the ipragliflozin group than
in the placebo group. The most common TEAEs (ipragliflozin
vs. placebo) were upper respiratory tract infections (9.2% [8/87]
vs. 12.0% [10/83]) and urinary tract infections (6.9% [6/87]
vs. 2.4% [2/83]). There were no episodes of hypoglycemia or
genital infection in either group. Polyuria occurred in 1.1%
(1/87) in the ipragliflozin group and pollakiuria occurred in
4.8% (4/83) in the placebo group.
Conclusion:
Ipragliflozin improved HbA1c and FPG, reduced
BW, WC, blood pressure and triglycerides, and was well
tolerated when used in combination with metformin in Asian
patients with type 2 diabetes.
Disclosure of Interest:
L.-M. Chuang Receiving support from:
Astellas Pharma Inc., Consultant with: Astellas Pharma Inc.,
K. W. Min Receiving support from: Astellas Pharma Inc., C.-H.
Lu Receiving support from: Astellas Pharma Inc., S. Kokubo
Employee with: Astellas Pharma Inc., S. Yoshida Employee
with: Astellas Pharma Inc., B. S. Cha Receiving support from:
Astellas Pharma Inc., Consultant with: Astellas Pharma Inc.
OP8
THE 2-WEEK FASTING GLUCOSE AS A PREDICTOR OF
GLYCEMIC RESPONSE TO ONCE-WEEKLY DULAGLUTIDE
1.5 MG
S. Gough
1
, G. Grunberger
2
, T. Forst
3
, V. Pechtner
4
,
R. Shaginian
5
, H. Wang
6
, L. Fernandez
7
.
1
University of Oxford
and Oxford University Hospitals NHS Trust, Oxford Centre for
Diabetes Endocrinology and Metabolism, Oxford, United Kingdom;
2
Grunberger Diabetes Institute, Bloomfield Hills, MI, United States;
3
Profil Mainz, Mainz, Germany;
4
Lilly Diabetes, Eli Lilly and
Company, Neuilly-Sur-Seine, France;
5
Lilly Diabetes, Eli Lilly
and Company, Houten, Netherlands;
6
Eli Lilly and Company,
Indianapolis, IN, United States;
7
Lilly Diabetes, Eli Lilly and
Company, Indianapolis, IN, United States
Background:
To assess whether laboratory fasting blood
glucose (FBG) in patients with type 2 diabetes mellitus (T2DM)
measured early in treatment with the once-weekly glucagon-
like peptide-1 (GLP-1) receptor agonist dulaglutide (DU) 1.5mg
predicts glycemic response.
Method:
Post-hoc
analyses were conducted separately for
2 double-blind, randomized Phase 3 studies (AWARD-5, in
combination with metformin, and AWARD-1, in combination
with metformin and pioglitazone) in patients with T2DM
assigned to once-weekly DU 1.5mg. In AWARD-5, FBG
values were categorized at baseline and week 2 as follows
(using tertiles): Low (L,
<
142mg/dL); Intermediate (I, 142 to
<
185mg/dL); and High (H, 185mg/dL). Treatment response
was assessed at week 12 (AWARD-5) or 13 (AWARD-1)
and 26 (AWARD-5, AWARD-1) by the following composite
efficacy endpoint (CEE): A1c
<
7.0% or A1c reduction from
baseline
>
0.8% (if baseline A1c
<
8.0%);
>
1.1% (if baseline
A1c 8.0% and
<
9.0%); or
>
1.6% (if baseline A1c 9.0%).
Association between FBG categories and the CEE was analyzed
using chi-square tests.
Result:
In AWARD-5, mean baseline A1c for DU 1.5mg (N= 304)
was 8.1%. At baseline, mean FBG was 176mg/dL, and 33%
(n = 99), 32% (n = 97), and 36% (n = 108) of patients had FBG in
L, I, and H categories, respectively. After 2 weeks of treatment,
mean FBG was 129mg/dL, and 68% (n = 208), 21% (n = 64), and
11% (n = 32) of patients had FBG in L, I, and H categories,
respectively. At week 26, mean A1c was 6.9%. There was a
strong association between FBG at week 2 and achieving the
CEE at week 26 (p
<
0.001). A significantly higher percentage of
patients in FBG category L (83% [172/208]) at week 2 met the
CEE at week 26 compared to patients in FBG categories I (61%
[39/64]), p
<
0.001, and H (34% [11/32]), p
<
0.001. CEE results
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