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PD-96
Efficacy and safety of once-weekly semaglutide versus
sitagliptin as add-on to metformin and/or thiazolidinediones
in subjects with T2D (SUSTAIN 2)
Francis CHOW
1
*, Bo AHRÉN
2
, Lluís MASMIQUEL COMAS
3
,
Harish KUMAR
4
, Mehmet SARGIN
5
, Julie DERVING KARSBØL
6
,
Sanja HALD JACOBSEN
6
.
1
Chinese University of Hong Kong, Shatin,
Hongkong;
2
Lund University, Lund, Sweden;
3
Hospital Quiron
Palmaplanas, Palma de Mallorca, Spain;
4
Amrita Institute of Medical
Sciences and Research Centre, Kochi, India;
5
Kartal Lufti Kirdar
Training and Research Hospital, Istanbul, Turkey;
6
Novo Nordisk A/
S, Søborg, Denmark
Semaglutide is a glucagon-like peptide-1 (GLP-1) analog in
development for the treatment of type 2 diabetes (T2D). This
study evaluated the efficacy, safety and tolerability of once-
weekly subcutaneous (s.c.) semaglutide versus sitagliptin in
subjects with T2D inadequately controlled on metformin
(MET) and/or thiazolidinediones (TZDs).
In this phase 3, double-blind, double-dummy study, 1231
subjects with T2D (HbA1c 7
–
10.5%) on MET and/or TZDs were
randomized 2:2:1:1 to once-weekly semaglutide 0.5 mg or
1.0 mg or once-daily sitagliptin 100 mg (sitagliptin/semaglu-
tide placebo arms were pooled in the analyses) for 56 weeks,
including 4
–
8 weeks of dose escalation. Primary endpoint was
change in HbA1c from baseline to Week 56. Secondary efficacy
endpoints included body weight (BW), blood pressure and
other glycemic parameters.
Mean HbA1c (baseline 8.1%) was reduced by 1.3% and 1.6%
with semaglutide 0.5 mg and 1.0 mg, respectively, versus 0.5%
with sitagliptin (estimated treatment difference versus sita-
gliptin [ETD]
−
0.77% and
−
1.06%; both p < 0.0001). HbA1c <7%
was achieved by 69% and 78% of 0.5 and 1.0 mg semaglutide-
treated subjects, respectively, versus 36% with sitagliptin;
corresponding proportions of subjects achieving HbA1c
≤
6.5%
were 53%, 66% and 20%. Mean BW (baseline 89.5 kg) was
reduced by 4.3 kg and 6.1 kg with semaglutide 0.5 mg and
1.0 mg versus 1.9 kg with sitagliptin (ETD
−
2.37 kg and
−
4.22 kg; both p < 0.0001). Improvements in other secondary
endpoints, including fasting plasma glucose and self-mon-
itored plasma glucose, were also observed with both doses of
semaglutide.
Proportions of subjects reporting adverse events (AEs) and
serious AEs (SAEs) were comparable between groups: 74.8%,
71.4% and 71.7% of subjects reported AEs and 7.3%, 7.3% and
7.1% reported SAEs with semaglutide 0.5 mg, 1.0 mg and
sitagliptin, respectively. Six fatal events occurred (2, 1 and 3
in the semaglutide 0.5 mg, 1.0 mg and sitagliptin study arms,
respectively). Proportions of subjects discontinuing due to
AEs were 8.1% for semaglutide 0.5 mg, 9.5% for semaglutide
1.0 mg and 2.9% for sitagliptin. The most frequent AEs were
gastrointestinal (GI), which were mainly mild or moderate.
Proportions of subjects reporting GI AEs in the semaglutide
0.5 mg, 1.0 mg and sitagliptin groups were 43.5%, 39.9% and
23.6%, respectively.
In conclusion, semaglutide (0.5 and 1.0 mg s.c. once weekly)
was superior to sitagliptin in improving glycemic control and
reducing BW in subjects with inadequately controlled T2D on
MET and/or TZDs. Semaglutidewas well toleratedwith a safety
profile similar to other GLP-1 receptor agonists.
PD-98
Efficacy and tolerability of gliclazide MR 60 mg in the
management of type 2 diabetes: Analysis of the EasyDia Trial
Marina SHESTAKOVA
1
*, Lawrence LEITER
2
.
1
Institute of Diabetes
Mellitus, Endocrinology Research Centre and M.I. Sechenov First
Moscow State Medical University, Russian Federation;
2
Divisions of
Endocrinology & Metabolism, Li Ka Shing Knowledge Institute,
St. Michael
’
s Hospital, University of Toronto, Canada
Background and aims:
Progressive intensification of
glucose-lowering with gliclazide modified release (MR) has
demonstrated long-term safety and renal protection in indivi-
duals with type 2 diabetes (T2D). The aim of these analyses
was to examine the efficacy and tolerability of the gliclazide
MR 60 mg regimen used in the EasyDia trial.
Materials and methods:
EasyDia was a 6-month international,
open-label study in which 7170 subjects with T2D were
prescribed 30
–
120 mg of gliclazide MR 60 mg, once daily, as a
first line, add-on, or switch from a previous oral glucose-
lowering treatment. Dosing uptitration was based on fasting
plasma glucose at months 1, 2, and 3. In the current analyses,
we examined the efficacy of gliclazide MR 60 mg at lowering
HbA1c and tolerability in various patient subgroups based on
their initial HbA1c, weight and glucose lowering treatment
(defined as newly diagnosed; add-on to metformin; or switch
from either another sulfonylurea or a DPP-4i).
Results:
After 6 months, the mean HbA1c was significantly
reduced across all the HbA1c subgroups (
−
1.03 ± 0.02% for 7
–
8%
subgroup,
−
1.55 ± 0.02% for 8
–
9% subgroup,
−
2.31 ± 0.04% for
9
–
10% subgroup, and
−
3.76 ± 0.06% for >10% subgroup).
Regarding treatment groups, the mean changes in HbA1c
between baseline and 6 months were:
−
2.13 ± 0.05% for newly
diagnosed,
−
1.76 ± 0.03% for add-on to metformin,
−
1.62 ±
0.06% when switched from another sulfonylurea, and
−
1.99 ±
0.30 when switched from a DPP-4i (all P < 0.01 vs baseline).
Weight neutrality was observed overall across the cohorts
between baseline and month 6, with a mean weight difference
of
−
1.34 ± 0.06 kg. These changes reflected significant weight
loss in patients with a BMI in the overweight (25
–
30) or
obese (
≥
30) range (
−
0.88 ± 0.07 and
−
2.24 ± 0.11 kg, respect-
ively; p < 0.01), with slight weight gain (+0.54 ± 0.16 kg) in
patients with normal BMI (18.5
–
24.9). Few patients experi-
enced hypoglycemia, with no differences observed between
the subgroups.
Conclusion:
Progressive titration of gliclazide MR 60 mg was
well tolerated and consistently effective in lowering HbA1c
across a broad range of patients with T2D. The main
determinant of the reduction in HbA1c was the level of
HbA1c at entry. Very large reductions were observed in
patients with initial HbA1c levels
≥
10%, while a smaller
adapted change was observed when the initial HbA1c was 7
–
8%. Additional reductions were observed when switched from
another sulfonylurea or DPP4-i. Concomitant weight loss was
also associated with baseline weight, with obese patients
losing significantly more weight than patients with a normal
BMI at baseline.
PD-100
Clinical effectiveness study of SGLT2 inhibitors as added-on
therapy for 149 insulin treated type 2 diabetes patients
Yuan-Ching LIU
1,2
, Cheng-Wei LIN
1
, I-Ying CHIU
1
,
Hsiao-Wei LU
1
, Cheng-Liang CHI
1
, Neng-Chun YU
1
*.
1
Neng-
Chun Diabetes Clinic, Yilan County,
2
Department of Nursing, School
of Medicine, National Taiwan University, Taipei, Taiwan
Background:
Sodium-glucose co-transporter 2 inhibitor
(SGLT2i) promotes renal glucose excretion through an insulin
independent mechanism. SGLT2i has shown ability to improve
A1C, body weight (BW), and blood pressure (BP) control. For
type 2 diabetes patients (T2DM) with insulin regimen, the
effectiveness of SGLT2i on themetabolic control was evaluated
in this study.
Methods:
A retrospective case note audit of patients was
performed in a diabetes clinic located at Yilan County, Taiwan.
SGLT2i was added to those adult T2DM patients with insulin
regimens. Datum of clinical parameters, self-monitor blood
glucose (SMBG), and adverse events were collected to analyze
the efficacy of SGLT2i for 6 months.
Results:
149 T2DM patients were selected in this study. The
average A1C, BMI, and BP at baselinewere 9.0%, 28.2 kg/m
2
, and
127.0/75.6 mmHg, respectively. 65.1% of patients used 10mg
daily dapagliflozin and 34.9% of patients used 10 mg daily
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65
–
S211
S122