Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

137 / 244

to improve glycemic control and body weight (BW) in T2DM
patients. This study leveraged EHR data to evaluate BW over
time among patients with T2DM receiving CANA in a real-
world setting.
Methods: Adult patients with ≥ 1 T2DM diagnosis and ≥ 12
months of clinical activity (baseline) before first CANA
prescription (index) were identified in the Cegedim Strategic
Data US EHR dataset. Paired t-tests were used to compare
baseline BW to BWat 3 and 12 months post-index. Proportions
of patients with a weight loss ≥5% from baseline were reported
overall and in patients with baseline BMI ≥ 30 kg/m2.
Results: A total of 16,163 CANA users were identified (35%
CANA 300 mg users, 48% female, mean age: 59 years, 76%
white, mean Charlson Comorbidity Index: 1.4, mean Diabetes
Complications Severity Index: 0.7). At baseline, 90% of patients
used ≥1 antihyperglycemic agent and 35% used insulin. Mean
exposure to CANA was 155.6 days. Among patients evaluated
at 3 months (N = 6,811; mean baseline BW= 102.9 kg), BW
decreased from baseline by 1.8 kg (P < 0.001) and 13.3% of
patients had a weight loss ≥5%. At 12 months (N = 1,288;
mean baseline BW= 103.8 kg), BW decreased from baseline by
2.6 kg (P < 0.001) and 25.8% of patients had a weight loss ≥5%.
Among patients with a baseline BMI ≥ 30 kg/m2, at 3 months
(N = 5,155; mean baseline BW= 110.3 kg) BW decreased by
2.1 kg (P < 0.001) and 13.6% of patients had a weight loss ≥5%;
at 12 months (N = 995; mean baseline BW= 110.8 kg), BW
decreased by 3.0 kg (P < 0.001) and 27.5% of patients had a
weight loss ≥5%.
Conclusions: Patients with T2DM treated with CANA in a real-
world setting experienced statistically significant weight loss
over time, in both the overall population and in patients with
BMI ≥ 30 kg/m 2.
PD-88
Semaglutide reduces appetite and energy intake, improves
control of eating and provides weight loss in subjects with
obesity
John BLUNDELL 1*, GrahamFINLAYSON1, Mads Buhl AXELSEN2,
Anne FLINT2, Catherine GIBBONS1, Trine KVIST2,
Eirik Quamme BERGAN 2, Julie HJERPSTED2. 1University of Leeds,
Leeds, United Kingdom; 2Novo Nordisk, Søborg, Denmark
Glucagon-like peptide-1 (GLP-1) therapy has the potential to
decrease body weight. Semaglutide is a human GLP-1 analog in
development for the treatment of type 2 diabetes. This study
examined the mechanisms of body weight loss compared with
placebo.
This double-blind, crossover study compared once-weekly
subcutaneous semaglutide (dose-escalated to 1.0 mg) with
placebo, in 30 subjects with obesity and without type 2
diabetes. The primary endpoint was ad libitum energy intake
during lunch (5 h after standardized breakfast) after 12 weeks
of treatment.
Ad libitumenergy intake with semaglutide vs placebowas 35%
lower at lunch (estimated treatment difference vs placebo
[ETD] −1255 kJ; 95% confidence interval [CI] –1707; –804), 18%
lower at evening meal (ETD –753 kJ; 95% CI –1469; –37) and 22%
lower after snack boxes (ETD –1028; 95% CI –1684; –372). Total
energy intake during ad libitummeals was significantly lower
(24%) with semaglutide vs placebo (ETD –3036 kJ; 95% CI –4209;
–1864). Resting metabolic rate also decreased 7% with sema-
glutide vs placebo (ETD –602 kJ/24 h [–959; –245]). Fasting
overall appetite score (visual analog scale) indicated reduced
appetite with semaglutide vs placebo (p = 0.0023), while
nausea ratings were similar. For semaglutide vs placebo, the
Control Of Eating Questionnaire indicated less hunger and
food cravings and better control of eating; the Leeds Food
Preference Task indicated a relatively lower preference for
high-fat vs low-fat foods. Mean body weight (overall mean at
baseline 101.3 kg; mean BMI 33.8 kg/m2) was reduced by
5.0 ± 2.4 (SD) kg with semaglutide treatment compared with a
body weight increase of 1.0 ± 2.4 kg with placebo, with
proportionally more fat than lean body mass lost.
In conclusion, semaglutide-induced body weight loss was
confirmed. Possible mechanisms are: reduced energy intake,
appetite and food cravings; better control of eating; and lower
relative preference for fatty, energy-dense foods.
PD-89
Semaglutide improves postprandial glucose and lipid
metabolism and delays first-hour gastric emptying in subjects
with obesity
John BLUNDELL1*, Mads Buhl AXELSEN2, Ashley BROOKS3,
Anne FLINT2, Trine KVIST2, Eirik Quamme BERGAN 2,
Julie HJERPSTED2. 1University of Leeds, Leeds, United Kingdom;
2Novo Nordisk, Søborg, Denmark; 3Covance Clinical Research Unit
Ltd, Leeds, United Kingdom
Glucagon-like peptide-1 (GLP-1) therapies may delay gastric
emptying and thus influence postprandial glucose and lipid
responses. Semaglutide is a human GLP-1 analog in develop-
ment for the treatment of type 2 diabetes. This study
investigated the effect of semaglutide on postprandial
glucose and lipid responses compared with placebo.
This double-blind, crossover study compared once-weekly
subcutaneous semaglutide (dose escalated to 1.0 mg) with
placebo in 30 subjects with obesity and without type 2 diabetes
(mean BMI 33.8 kg/m2). After each 12-week treatment period,
subjects were given a standardised breakfast or a standardised
fat-rich breakfast. Fasting glucose metabolism was assessed
prior to standardised breakfast, and postprandial glucose
metabolism and gastric emptying were assessed after.
Fasting lipid metabolism was assessed prior to standardised
fat-rich breakfast, and postprandial lipid metabolism after.
After 12 weeks of treatment, fasting concentrations of
insulin were higher with semaglutide vs placebo (estimated
treatment ratio [ETR] 1.45; 95% confidence interval [CI] 1.20;
1.75), as was C-peptide (ETR 1.35; 95% CI 1.20; 1.52). Fasting
concentrations of glucose were lower with semaglutide vs
placebo (ETR 0.95; 95% CI 0.91; 0.98), as were glucagon
(ETR 0.86; 95% CI 0.75; 0.98), triglycerides (ETR 0.88; 95% CI
0.80; 0.98) and very low density lipoprotein (ETR 0.79; 95% CI
0.66; 0.95). After a standardized breakfast, postprandial glucose
levels were lower with semaglutide vs placebo (estimated
treatment difference [ETD]; −1.34 mm*h/L 95% CI − 2.42; −0.27),
as were insulin (ETD −921 pmol*h/L; 95% CI − 1461; −381) and
C-peptide levels (ETD −1.42 nmol*h/L; 95% CI −2.33; −0.51).
After a standardized fat-rich breakfast, triglycerides were
lower for semaglutide vs placebo (ETD −4.51 mmol*h/L; 95%
CI −6.15; −2.87); as were very low density lipoprotein (ETD
−1.17 mmol*h/L; 95% CI −2.03; −0.32) and apolipoprotein B48
(which facilitates lipid absorption in the intestine) levels (ETD
−0.0455 g*h/L; 95% CI −0.0690; −0.0220). No statistical differ-
ence between treatments was shown for the overall rate of
postprandial gastric emptying (AUC0-5h); however, for sema-
glutide vs placebo, gastric emptying was delayed during the
first hour.
In conclusion, semaglutide improves fasting and postprandial
glucose levels, as well as fasting and postprandial lipid
metabolism, vs placebo, and delays gastric emptying during
the first hour.
PD-90
Renal effects of canagliflozin in patients with Type 2 diabetes
Yip Fong WONG1*, Yanli SHAO1, Chee Fang SUM 1. 1Diabetes
Centre, Khoo Teck Puat Hospital, Singapore
Background: Canagliflozin, a sodium glucose co-transporter-2
(SGLT2) inhibitor, reduces blood glucose level in Type 2
diabetes (T2DM) patients by lowering the renal threshold for
glucose, thereby increasing urinary glucose excretion. With
the recent introduction of canagliflozin into the formulary,
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211 S119