Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study

Abstract

Background: Central obesity is associated with increased risk of cardiometabolic disease. Weight loss reduces lean muscle mass, potentially impacting resting energy expenditure and/or physical functioning. This analysis of the STEP 1 trial evaluated the impact of subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, on body composition in adults with overweight/obesity using dual energy X-ray absorptiometry (DEXA).
Methods: In STEP 1, 1961 adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without diabetes, were randomized to s.c. semaglutide 2.4 mg once-weekly or matched placebo (2:1) for 68 weeks, plus lifestyle intervention. Participants with BMI ≤40 kg/m2 from 9 sites were eligible for the substudy. Total fat mass, total lean body mass and regional visceral fat mass were measured using DEXA at screening and week 68; visceral fat mass was calculated in the L4 region (both males/females), android region (males), or gynoid region (females), depending on site scanner methodology. Proportions of total fat and lean body mass are shown relative to total body mass; proportion of visceral fat mass is expressed relative to region assessed.
Results: This analysis included 140 participants (semaglutide n=95; placebo n=45) (mean weight 98.4 kg, BMI 34.8 kg/m2; 76% female). Baseline body composition was similar in those receiving semaglutide and placebo (total fat mass proportion: 43.4% vs 44.6%; regional visceral fat mass proportion: 33.8% vs 36.3%; total lean body mass proportion: 53.9% vs 52.7%; respectively). Percentage change in body weight from baseline to week 68 was -15.0% with semaglutide vs -3.6% with placebo. This resulted in reductions from baseline with semaglutide in total fat mass (-19.3%) and regional visceral fat mass (-27.4%), leading to 3.5%-point and 2.0%-point reductions in the proportions of total fat mass and visceral fat mass, respectively. Total lean body mass decreased from baseline (-9.7%); however, the proportion relative to total body mass increased by 3.0%-points. An increasing improvement in lean body mass:fat mass ratio was seen with semaglutide with increasing weight loss from baseline to week 68 (continuous data). Overall, the ratio increased from baseline (1.34 [95% CI: 1.22, 1.47]) to week 68 by 0.23 [0.14, 0.32], with greater improvement in those with ≥15% weight loss (n=44; 0.41 [0.28, 0.53]) vs <15% weight loss (n=39; 0.03 [-0.05, 0.12]) (observed, dichotomized data; no imputation for missing data). There were no major changes in body composition with placebo from baseline to week 68.
Conclusion: In adults with overweight/obesity, semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass, and an increased proportion of lean body mass. Greater weight loss was associated with greater improvement in body composition (lean body mass:fat mass ratio).

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A16
A16 | Journal of the Endocrine Society | doi: 10.1210/jendso/bvab048
J Endocrine Soc, Volume 5, Issue Supplement_1, April-May 2021
samples. Although CD8+/CD45+/perf-- and CD56+/CD45+/
perf-- cells were identified. Next, we analysed the same
cells for cytotoxic activation by 107a. The percentage of
107a positivity was low in CD 8+ (7% and 4 % respectively
in cases and control) and CD 56+ cells (10% and 9 % re-
spectively in cases and control),Although clinically type 2
DM subjects were obese and had inflammation (i.e higher
hsCRP), there was no difference in VAT activation of im-
mune cells studied. Also, we could not delineate perforin in
any of the samples. Conclusion: Taken together this work
suggests VAT T cell immune milieu in human Type 2 DM
is different from mouse model. It is neither characterised
by perforin deficiency nor activation of T cell/NK cell. This
study points towards the probability that, the role of T cell/
NK cells in human VAT infiltration could be fundamentally
different from mice models. Further studies should be fo-
cussed on functional characteristics of these cells and in-
teraction with VAT macrophages. References 1. Xavier
S.Revelo etal Diabetes 2015;64:90–103 2.Wetzels S etal J
Vis Exp.2018 Mar 6;(133):57319.
Adipose Tissue, Appetite, andObesity
INTEGRATED PHYSIOLOGY OF OBESITY AND
METABOLIC DISEASE
Impact of Morbid Obesity on Patients With
Hypertriglyceridemia Induced Acute Pancreatitis
GarimaPudasaini, MD1, HafeezShaka, MD2,
AchebeIkechukwu, MD1, JenniferChiagoziemAsotibe,
M.D3, EmmanuelPalomeraTejeda, MD4,
MuhammadSheharyarWarraich, MD1, EssamRashad, MD1.
1john h.stroger hospital of cook county, chicago, IL, USA, 2John
H Stroger Jr Hospital of Cook County, Chicago, IL, USA, 3COOK
COUNTY HOSPITAL, CHICAGO, IL, USA, 4COOK COUNTY
HOSPITAL, Chicago, IL, USA.
Introduction: Obesity is reportedly associated with
worse outcome in patients with acute pancreatitis (AP).
However, AP has varying etiologies. Hypertriglyceridemia
induced acute pancreatitis (HTGP) has sociodemographic
variations compared to AP from biliary stones or alcohol.
This study aimed to determine the impact of obesity on
outcomes of patients with HTGP. Methods: This was a
retrospective cohort study of the combined Nationwide
Inpatient Sample database for 2016 and 2017. Hospital
discharges of patients 18years and over with HTGP were
included. This cohort was divided based on presence of co-
morbid obesity into three groups- patients without obe-
sity, mild-moderate obesity (MMO) (BMI: 30.0 - 39.9) and
morbid obesity (MO) (BMI >=40.0). Primary outcome was
inpatient mortality. Secondary outcomes included length
of hospital stay (LOS), total hospital charges (THC), dis-
charge diagnoses of hypocalcemia, sepsis, septic shock,
acute renal failure (AKI) and acute respiratory failure
(ARF). Multivariate regression analysis was used to ad-
just for patients’ sociodemographic factors, Charlson co-
morbidity index as well as hospital characteristics as
confounders. Results: Atotal of 104,465 hospitalizations
were principally for HTGP, accounting for 18.2% of
patients with acute pancreatitis during the study period.
Of the patients with HTGP, 13.7% and 10.9% of these
patients classified as having MMO and MO respectively.
Patients with obesity were significantly younger than
patients without obesity.
In patients with MO, there was higher odds of mortality
(aOR=1.83, 95% CI: 1.090 – 3.083, p=0.022), while there
was no difference in mortality in patients with MMO (aOR
1.09 95% CI: 0.609– 1.940, p=0.777), both compared with
patients without obesity. Patients with MO had increased
mean LOS of 0.5days (95% CI: 0.3– 0.7, p<0.001) as well
as increased THC of $3977 (95% CI: 1467– 6487, p=0.002)
compared to those without obesity. There was no differ-
ence in mortality, THC and LOS in patients with MMO.
Morbidly obese patients also had increased odds of septic
shock (aOR=2.27, 95% CI: 1.297 – 3.972, p=0.007), AKI
(aOR=1.28, 95% CI: 1.120 – 1.459, p<0.001), and ARF
(aOR=1.94, 95% CI: 1.491 – 2.524, p<0.001). Conclusion:
Morbid obesity is associated with higher mortality and poor
outcomes in patient with hypertriglyceridemia induced
pancreatitis.
Adipose Tissue, Appetite, andObesity
INTEGRATED PHYSIOLOGY OF OBESITY AND
METABOLIC DISEASE
Impact of Semaglutide on Body Composition in
Adults With Overweight or Obesity: Exploratory
Analysis of the STEP 1Study
JohnPHWilding, DM, FRCP1, RachelL.Batterham, MD,
PhD2, SalvatoreCalanna, PhD3, LucF.VanGaal, MD,PhD4,
BarbaraM.McGowan, MD, PhD5, JulioRosenstock,
MD6, MarieTDTran, MD, PhD3, SeanWharton, MD,
PharmD7, KoutaroYokote, MD, PhD8, NielsZeuthen, MSc3,
RobertF.Kushner, MD9.
1Obesity and Endocrinology Research, Department of
Cardiovascular and Medicine, Institute of Life Course and
Medical Sciences, University of Liverpool, Liverpool, United
Kingdom, 2University College London Centre for Obesity
Research, Division of Medicine, University College London
and National Institute of Health Research, UCLH Biomedical
Research Centre and Centre for Weight Management and
Metabolic Surgery, UCLH, London, United Kingdom, 3Novo
Nordisk A/S, Søborg, Denmark, 4Department of Endocrinology,
Diabetology and Metabolism, Antwerp University Hospital,
University of Antwerp, Edegem, Belgium, 5Department of
Diabetes and Endocrinology, Guy’s and St Thomas’ NHS
Foundation Trust, London, United Kingdom, 6Dallas Diabetes
Research Center at Medical City, Dallas, TX, USA, 7York
University, McMaster University and Wharton Weight
Management Clinic, Toronto, ON, Canada, 8Department of
Endocrinology, Hematology and Gerontology, Graduate School
of Medicine, Chiba University and Department of Diabetes,
Metabolism and Endocrinology, Chiba University Hospital, Chiba,
Japan, 9Division of Endocrinology, Feinberg School of Medicine,
Northwestern University, Chicago, IL, USA.
Background: Central obesity is associated with increased
risk of cardiometabolic disease. Weight loss reduces lean
muscle mass, potentially impacting resting energy ex-
penditure and/or physical functioning. This analysis of the
STEP 1 trial evaluated the impact of subcutaneous (s.c.)
semaglutide, a glucagon-like peptide-1 analogue, on body
composition in adults with overweight/obesity using dual
energy X-ray absorptiometry(DEXA).
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A17
doi: 10.1210/jendso/bvab048 | Journal of the Endocrine Society | A17
J Endocrine Soc, Volume 5, Issue Supplement_1, April-May 2021
Methods: In STEP 1, 1961 adults aged ≥18 years with
body mass index (BMI) ≥27kg/m2 with ≥1 weight-related
comorbidity or BMI ≥30 kg/m2, without diabetes, were
randomized to s.c. semaglutide 2.4 mg once-weekly or
matched placebo (2:1) for 68 weeks, plus lifestyle interven-
tion. Participants with BMI ≤40kg/m2 from 9 sites were
eligible for the substudy. Total fat mass, total lean body
mass and regional visceral fat mass were measured using
DEXA at screening and week 68; visceral fat mass was
calculated in the L4 region (both males/females), android
region (males), or gynoid region (females), depending on
site scanner methodology. Proportions of total fat and lean
body mass are shown relative to total body mass; propor-
tion of visceral fat mass is expressed relative to region
assessed.
Results: This analysis included 140 participants
(semaglutide n=95; placebo n=45) (mean weight 98.4kg,
BMI 34.8 kg/m2; 76% female). Baseline body compo-
sition was similar in those receiving semaglutide and
placebo (total fat mass proportion: 43.4% vs 44.6%; re-
gional visceral fat mass proportion: 33.8% vs 36.3%;
total lean body mass proportion: 53.9% vs 52.7%; respec-
tively). Percentage change in body weight from baseline
to week 68 was -15.0% with semaglutide vs -3.6% with
placebo. This resulted in reductions from baseline with
semaglutide in total fat mass (-19.3%) and regional vis-
ceral fat mass (-27.4%), leading to 3.5%-point and 2.0%-
point reductions in the proportions of total fat mass and
visceral fat mass, respectively. Total lean body mass
decreased from baseline (-9.7%); however, the proportion
relative to total body mass increased by 3.0%-points. An
increasing improvement in lean body mass:fat mass ratio
was seen with semaglutide with increasing weight loss
from baseline to week 68 (continuous data). Overall, the
ratio increased from baseline (1.34 [95% CI: 1.22, 1.47])
to week 68 by 0.23 [0.14, 0.32], with greater improvement
in those with ≥15% weight loss (n=44; 0.41 [0.28, 0.53])
vs <15% weight loss (n=39; 0.03 [-0.05, 0.12]) (observed,
dichotomized data; no imputation for missing data). There
were no major changes in body composition with placebo
from baseline to week68.
Conclusion: In adults with overweight/obesity,
semaglutide 2.4mg was associated with reduced total fat
mass and regional visceral fat mass, and an increased pro-
portion of lean body mass. Greater weight loss was associ-
ated with greater improvement in body composition (lean
body mass:fat mass ratio).
Adipose Tissue, Appetite, andObesity
INTEGRATED PHYSIOLOGY OF OBESITY AND
METABOLIC DISEASE
Incidence of Insulin Resistance in Obese Adolescent
of Type-2 Diabetes Mellitus Patients
FarrukhJavaid, PGR Endocrinology1, RukhshanKhurshid,
Assitant Professor Biochemistry1, HumaAshraf, Associate
Professor Biochemistry2, AbeeraMazhar, PGR Pediatrics3,
LubnaAmir, Associate Professor Pharmacology4.
1Services Hospital / Shalamar Hospital, Lahore, Pakistan, 2CMH,
Lahore, Pakistan, 3Mayo Hospital, Lahore, Pakistan, 4FMH,
Lahore, Pakistan.
Background: Insulin resistance is a reduced response of
tissue to insulin-mediated action on cells. It may be due
to many reasons, including the surplus of adipose tissue,
which cause a resistance of insulin. Aims and Objectives:
To find the incidence of insulin resistance in obese adoles-
cent of type-2 diabetes mellitus patients.
Material and Methods: The study involved 50 adolescents
aged 14–20years old. Adolescents with BMI > 26.0 Kg/m2
were included in the study. Levels of fasting blood sugar,
Hb A1c and serum insulin were estimated. The index of
Homeostatic model assessment for insulin resistance or
HOMA-IR was calculated. The cut-off value of HOMA-IR
was > 3.16 for both genders.
Results: It was observed that the values of BMI and level of
fasting blood sugar of first degree relatives of diabetics was
significantly higher as compared to their controls. Levels
of both blood HbA1c and serum insulin were increased but
significant difference was observed only in case of serum
insulin when compared with their controls.
Conclusion: Obesity in adolescents of first degree relatives
of diabetics shows a major reason of insulin resistance. The
incidence of insulin resistance in obese adolescents signals
a perturbing trend for the burden of type 2 diabetes in our
country.
Adipose Tissue, Appetite, andObesity
INTEGRATED PHYSIOLOGY OF OBESITY AND
METABOLIC DISEASE
Insulin Resistance Moderates the Association
Between BMI and Metabolic Syndrome Severity in
Women 4–10 Years After Pregnancy, Independent of
Gestational DiabetesStatus
MakenzieCallahan, MS1, SamanthaMartin, PhD1,
JessicaBahorski, PhD2, GregoryPavela, PhD1, WTimothyGarvey,
MD1, PaulaC.Chandler-Laney, PhD1.
1University of Alabama at Birmingham, Birmingham, AL, USA,
2Florida State University, Tallahassee, FL, USA.
Objective: Obesity and gestational diabetes mellitus (GDM)
increase the risk for metabolic syndrome (MetS). Insulin
resistance (IR) is associated with obesity, contributes to
risk for GDM, and persists after pregnancy even when glu-
cose tolerance returns. Further, IR may enhance the risk
of MetS associated with obesity and GDM. The purpose of
this study was to test the hypothesis that IR moderates the
relationship between BMI and MetS severity 4–10 years
after pregnancy, independent of prior GDM, such that the
positive association between BMI and MetS severity is
stronger among women with greater IR. Methods: This
hypothesis was tested in a secondary analysis of data col-
lected from women enrolled in a study of the intergenera-
tional transmission of obesity, 4–10years after the index
pregnancy. Recruitment in the parent study was stratified
to include women with normal weight without GDM (NW),
overweight or obesity without GDM (OwOB), and women
with GDM during the index pregnancy. Standard clinical
procedures were used to measure height, weight, waist cir-
cumference and blood pressure, and a fasting blood draw
was obtained with which to measure glucose, insulin,
triglycerides, and HDL-cholesterol. MetS was evaluated as
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