Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

cholinesterasewere significantly correlatedwith the reduction

of SSPG.

Conclusion:

Short-term tofogliflozin treatment significantly

improved 24-h glucose profiles. The decline in body weight

primarily resulted from the decrease in body fat. However, the

risk of dehydration was not excluded because the subjects of

this study were urged to drink adequate water during the

treatment. Insulin sensitivity significantly improved likely due

to the decrease in body fat mass. In addition, the improvement

of hepatic steatosis may be involved in the amelioration of

insulin resistance.

OL05-3

Efficacy and safety of once-weekly semaglutide vs exenatide

ER after 56Weeks in subjects with type 2 diabetes (SUSTAIN 3)

Andrew AHMANN

, Matthew CAPEHORN

Guillaume CHARPENTIER

, Francesco DOTTA

Elena HENKEL

, Ildiko LINGVAY

, Anders GAARSDAL HOLST

Miriam ANNETT

, Vanita ARODA

Harold Schnitzer Diabetes

Health Center, OR, United States of America;

Rotherham Institute for

Obesity, Rotherham, United Kingdom;

Centre Hospitalier Sud

Francilien, Corbeil-Essonnes, France;

University of Siena, Siena,

Italy;

Center for Clinical Studies, Technical University, Dresden,

Germany;

UT Southwestern Medical Center, Dallas, TX, United

States of America;

Novo Nordisk A/S, Søborg, Denmark,

Novo

Nordisk Inc., NJ,

MedStar Health Research Institute, Hyattsville, MD,

United States of America

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 semaglutide versus exenatide extended-

release (ER) in subjects with T2D inadequately controlled on 1

–

2 oral antidiabetic drugs (OADs: metformin, sulfonylureas and

thiazolidinediones).

In this phase 3, open-label study, 813 adults with T2D (HbA1c

–

10.5%) were randomized 1:1 to once-weekly semaglutide

1.0 mg or once-weekly exenatide ER 2.0 mg for 56 weeks. The

primary endpoint was change in HbA1c from baseline to Week

56. Secondary efficacy endpoints included change in body

weight (BW), blood pressure and other glycemic parameters.

Baseline characteristics were similar in both arms; overall

mean age 56.6 years, duration of T2D 9.2 years. Mean HbA1c

(overall baseline mean 8.3%) was reduced by 1.5% with

semaglutide and 0.9% with exenatide ER (estimated treatment

difference vs exenatide ER [ETD]

–

0.62%; p < 0.0001). HbA1c <7%

was achieved by 67% of semaglutide-treated subjects versus

40% with exenatide ER; 47% and 22% achieved HbA1c

≤

6.5%,

respectively. Mean BW (overall baseline mean 95.8 kg) was

reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide

ER (ETD

–

3.73 kg; p < 0.0001).

Adverse event (AE) rates were comparable between groups:

75.0% and 76.3% of subjects reported AEs with semaglutide

and exenatide ER, respectively. Serious AEs were reported by

9.4% of subjects receiving semaglutide and 5.9% of subjects

receiving exenatide ER (spread over multiple system organ

classes). Two fatal events were reported in the semaglutide

arm (both advanced stage neoplasms considered unrelated to

treatment). The proportion of subjects discontinuing treat-

ment due to AEs was 9.4% for semaglutide and 7.2% for

exenatide ER. Themost frequent AEs were gastrointestinal (GI),

which were mainly mild or moderate in severity. GI AEs were

reported by 41.8% and 33.3% of subjects receiving semaglutide

and exenatide ER, respectively; 22.3% and 11.9% for nausea,

11.4% and 8.4% for diarrhea and 7.2% and 6.2% for vomiting.

The proportion of subjects reporting nausea diminished over

time in both groups. Injection site reactions were reported by

1.2% of subjects receiving semaglutide and 22.0% of subjects

receiving exenatide ER.

In conclusion, once-weekly subcutaneous semaglutide

1.0 mg was superior to exenatide ER 2.0 mg in improving

glycemic control and reducing BW in subjects with T2D

inadequately controlled on 1

–

2 OADs. Semaglutide was well

tolerated, with a safety profile similar to that of other GLP-1

receptor agonists.

OL05-4

Efficacy and safety of once-weekly semaglutide versus once-

daily insulin glargine in insulin-naïve subjects with type 2

diabetes (SUSTAIN 4)

Vanita ARODA

, Stephen BAIN

, Bertrand CARIOU

Milivoj PILETIC

, Ludger ROSE

, Eirik Quamme BERGAN

Jeppe ZACHO

, J Hans DEVRIES

MedStar Health Research

Institute, Hyattsville, MD, United States of America;

School of

Medicine, Swansea University, Wales, United Kingdom;

CHU

Nantes, l

’

Institut du Thorax, Nantes, France;

General Hospital, Novo

Mesto, Slovenia;

Münster Institute for Diabetes Research, Münster,

Germany;

Novo Nordisk A/S, Søborg, Denmark;

Academic Medical

Center, University of Amsterdam, Netherlands

This trial evaluated the efficacy and safety of subcutaneous (s.

c.) semaglutide versus insulin glargine (IGlar) in insulin-naïve

subjects with T2D.

In this phase 3a, randomized, open-label study, 1082 adults

with T2D (HbA1c 7

–

10%) received semaglutide 0.5 mg (n = 362)

or 1.0 mg (n = 360) once weekly or IGlar (n = 360; starting dose

10 IU/day) once daily for 30 weeks, added to stable metformin

−

sulfonylurea (SU). Investigators were instructed to titrate

to a pre-breakfast self-monitored plasma glucose (SMPG)

target of 4.0

–

5.5 mmol/L. Primary endpoint was change in

HbA1c from baseline to Week 30.

Mean HbA1c (baseline 8.2%) was reduced with semaglutide 0.5

and 1.0 mg by 1.2% and 1.6% versus 0.8% with IGlar (estimated

treatment difference versus IGlar [ETD]

–

0.38% and

–

0.81%;

p < 0.0001 for both). Mean IGlar dose at Week 30 was 29.2 IU/

day. HbA1c <7% was achieved by 57.5% and 73.3% of 0.5 and

1.0 mg semaglutide-treated subjects, respectively, versus

38.1% with IGlar. HbA1c

≤

6.5% was achieved by 37.3%, 54.2%

and 17.5% of subjects, respectively. Mean fasting plasma

glucose (baseline 9.7 mmol/L) was reduced with semaglutide

0.5 and 1.0 mg by 2.1 and 2.7 mmol/L versus 2.1 mmol/L with

IGlar (ETD 0.07 mmol/L [p = 0.7] and

–

0.61 mmol/L [p = 0.0002]).

Mean 8-point SMPG (baseline 10.9 mmol/L) was reduced by 2.4,

2.9 and 2.4 mmol/L, respectively (ETD

–

0.07 mmol/L [p = 0.6]

and

–

0.58 mmol/L [p < 0.0001]).

Mean body weight (BW; baseline 93.4 kg) decreased with

semaglutide 0.5 and 1.0 mg by 3.5 and 5.2 kg versus a 1.2 kg

increase with IGlar (ETD

–

4.62 kg and

–

6.34 kg; p < 0.0001 for

both).

Proportions of subjects reporting adverse events (AEs) were

69.9%, 73.3% and 65.3% with semaglutide 0.5, 1.0 mg and IGlar,

respectively; 6.1%, 4.7% and 5.0% reported serious AEs. Fatal

AEs were reported in 4 semaglutide subjects and 2 IGlar

subjects. Discontinuation due to AEs occurred in 5.5%, 7.5%

and 1.1% of patients, respectively. The majority of disconti-

nuations with semaglutide were due to gastrointestinal (GI)

AEs; mild, transient GI AEs were the most common AEs with

semaglutide. Proportions of subjects reporting GI AEs were:

21.3%, 22.2% and 3.6% for nausea; 16.3%, 19.2% and 4.4% for

diarrhea; and 6.6%, 10.3% and 3.1% for vomiting.

In conclusion, semaglutide (0.5 and 1.0 mg s.c. once weekly)

provided superior glycemic control and BW reduction versus

IGlar in patients with T2D treated with metformin +/

−

SU.

Semaglutide was well tolerated with a safety profile similar to

other GLP-1 receptor agonists.

Oral Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S40

–

S64

S51