Nejmoa2032183 - STEP 1

new england
The
journal of medicine
established in 1812 March 18, 2021 vol. 384 no. 11
Once-Weekly Semaglutide in Adults with Overweight

or Obesity
John P.H. Wilding, D.M., Rachel L. Batterham, M.B., B.S., Ph.D., Salvatore Calanna, Ph.D., Melanie Davies, M.D.,
Luc F. Van Gaal, M.D., Ph.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Barbara M. McGowan, M.D., Ph.D.,
Julio Rosenstock, M.D., Marie T.D. Tran, M.D., Ph.D., Thomas A. Wadden, Ph.D., Sean Wharton, M.D., Pharm.D.,
Koutaro Yokote, M.D., Ph.D., Niels Zeuthen, M.Sc., and Robert F. Kushner, M.D., for the STEP 1 Study Group*
a bs t r ac t
BACKGROUND
Obesity is a global health challenge with few pharmacologic options. Whether The authors’ affiliations are listed in the
adults with obesity can achieve weight loss with once-weekly semaglutide at a dose Appendix. Address reprint requests to
Dr. Kushner at Northwestern University
of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. Feinberg School of Medicine, 645 N.
METHODS Michigan Ave., Suite 530, Chicago, IL
60611, or at rkushner@northwestern.edu.
In this double-blind trial, we enrolled 1961 adults with a body-mass index (the
weight in kilograms divided by the square of the height in meters) of 30 or greater *A complete list of investigators in the
STEP 1 trial is provided in the Supple-
(≥27 in persons with ≥1 weight-related coexisting condition), who did not have mentary Appendix, available at NEJM.org.
diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment
with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus This article was published on February 10,
2021, at NEJM.org.
lifestyle intervention. The coprimary end points were the percentage change in body
weight and weight reduction of at least 5%. The primary estimand (a precise descrip- N Engl J Med 2021;384:989-1002.
DOI: 10.1056/NEJMoa2032183
tion of the treatment effect reflecting the objective of the clinical trial) assessed Copyright © 2021 Massachusetts Medical Society.
effects regardless of treatment discontinuation or rescue interventions.
RESULTS
The mean change in body weight from baseline to week 68 was −14.9% in the
semaglutide group as compared with −2.4% with placebo, for an estimated treatment
difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5;
P<0.001). More participants in the semaglutide group than in the placebo group
achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]),
10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28
[4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body
weight from baseline to week 68 was −15.3 kg in the semaglutide group as com-
pared with −2.6 kg in the placebo group (estimated treatment difference, −12.7 kg;
95% CI, −13.7 to −11.7). Participants who received semaglutide had a greater im-
provement with respect to cardiometabolic risk factors and a greater increase in
participant-reported physical functioning from baseline than those who received
placebo. Nausea and diarrhea were the most common adverse events with sema-
glutide; they were typically transient and mild-to-moderate in severity and subsided
with time. More participants in the semaglutide group than in the placebo group
discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).
CONCLUSIONS
In participants with overweight or obesity, 2.4 mg of semaglutide once weekly
plus lifestyle intervention was associated with sustained, clinically relevant reduc-
tion in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number,
NCT03548935).
n engl j med 384;11 nejm.org March 18, 2021 989
The New England Journal of Medicine
Downloaded from nejm.org at NARESUAN UNIVERSITY on July 7, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
The n e w e ng l a n d j o u r na l of m e dic i n e
O
besity is a chronic disease and ica. The sponsor (Novo Nordisk) designed the trial
global public health challenge.1-3 Obesity and oversaw its conduct. The design has been
can lead to insulin resistance, hyperten- published previously.15 The trial was conducted
sion, and dyslipidemia,4 is associated with com- in accordance with the principles of the Declara-
A Quick Take
plications such as type 2 diabetes, cardiovascular tion of Helsinki and Good Clinical Practice
is available at disease, and nonalcoholic fatty liver disease,2,5 guidelines. The protocol (available with the full
NEJM.org and reduces life expectancy.6 More recently, obe- text of this article at NEJM.org) was approved by
sity has been linked to increased numbers of hos- an independent ethics committee or institutional
pitalizations, the need for mechanical ventilation, review board at each study site. Investigators were
and death in persons with coronavirus disease responsible for data collection, and the sponsor
2019 (Covid-19).7,8 undertook site monitoring, data collation, and
Although lifestyle intervention (diet and exer- analysis. All authors had full access to study data,
cise) represents the cornerstone of weight man- participated in drafting the manuscript (assisted
agement,1,2 sustaining weight loss over the long by a sponsor-funded medical writer), approved its
term is challenging.9 Clinical guidelines suggest submission for publication, and vouch for the
adjunctive pharmacotherapy, particularly for adults accuracy and completeness of the data and for
with a body-mass index (BMI, the weight in kilo- the fidelity of the trial to the protocol.
grams divided by the square of the height in
meters) of 30 or greater, or 27 or greater in Participants
persons with coexisting conditions.1,2,10 However, We enrolled adults (18 years of age or older) with
the use of available medications remains limited one or more self-reported unsuccessful dietary
by modest efficacy, safety concerns, and cost.3 efforts to lose weight and either a BMI of 30 or
Semaglutide is a glucagon-like peptide-1 (GLP-1) greater or a BMI of 27 or greater with one or
analogue that is approved, at doses up to 1 mg more treated or untreated weight-related coexist-
administered subcutaneously once weekly, for the ing conditions (i.e., hypertension, dyslipidemia,
treatment of type 2 diabetes in adults and for re- obstructive sleep apnea, or cardiovascular disease).
ducing the risk of cardiovascular events in per- A subgroup of participants with a BMI of 40 or
sons with type 2 diabetes and cardiovascular dis- less underwent dual-energy x-ray absorptiometry
ease.11 Semaglutide induced weight loss in persons (DXA) to assess body composition. All participants
with type 2 diabetes and in adults with obesity provided written informed consent. Key exclu-
who were participants in a phase 2 trial,12-14 sion criteria were diabetes, a glycated hemoglobin
findings that supported further investigation. level of 48 mmol per mole (6.5%) or greater, a
The global phase 3 Semaglutide Treatment Ef- history of chronic pancreatitis, acute pancreatitis
fect in People with Obesity (STEP) program aims within 180 days before enrollment, previous sur-
to evaluate the efficacy and safety of semaglu- gical obesity treatment, and use of antiobesity
tide administered subcutaneously at a dose of medication within 90 days before enrollment. A
2.4 mg once weekly in persons with overweight full list of the eligibility criteria is provided in the
or obesity, with or without weight-related com- Supplementary Appendix, available at NEJM.org.
plications.15
This 68-week trial evaluated the efficacy and Procedures
safety of semaglutide as compared with placebo Participants were randomly assigned in a 2:1 ra-
as an adjunct to lifestyle intervention for reducing
tio, through the use of an interactive Web-based
body weight and meeting other related end points response system, to receive semaglutide at a
in adults with overweight or obesity and without dose of 2.4 mg administered subcutaneously
diabetes. once a week for 68 weeks or matching placebo,
in addition to lifestyle intervention; this 68-week
period was followed by a 7-week period without
Me thods
receipt of semaglutide or placebo or lifestyle
Trial Design and Oversight intervention. Semaglutide, administered with a
We conducted a randomized, double-blind, pla- prefilled pen injector, was initiated at a dose of
cebo-controlled trial at 129 sites in 16 countries 0.25 mg once weekly for the first 4 weeks, with
in Asia, Europe, North America, and South Amer- the dose increased every 4 weeks to reach the
990 n engl j med 384;11 nejm.org March 18, 2021

Semaglutide in Adults with Overweight or Obesity
maintenance dose of 2.4 mg weekly by week 16 Statistical Analysis

(lower maintenance doses were permitted if A sample size of 1950 participants provided an
participants had unacceptable side effects with effective power of 99% for the coprimary and
the 2.4-mg dose) (Fig. S1 in the Supplementary confirmatory secondary end points, tested in a
Appendix). Participants received individual coun- prespecified hierarchical order. Efficacy end points
seling sessions every 4 weeks to help them were analyzed in the full analysis population (all
adhere to a reduced-calorie diet (500-kcal defi- randomly assigned participants according to the
cit per day relative to the energy expenditure intention-to-treat principle); safety end points
estimated at the time they underwent random- were analyzed in the safety analysis population
ization) and increased physical activity (with (all randomly assigned participants exposed to
150 minutes per week of physical activity, such at least one dose of semaglutide or placebo).
as walking, encouraged). Both diet and activity Observation periods included the in-trial period
were recorded daily in a diary or by use of a (the time from random assignment to last con-
smartphone application or other tools and were tact with a trial site, regardless of treatment
reviewed during counseling sessions. Participants discontinuation or rescue intervention) and the
discontinuing treatment prematurely remained on-treatment period. All results from statistical
in the trial. analyses were accompanied by a two-sided 95%
confidence interval and corresponding P values
End Points and Assessments (with significance defined as P<0.05). Supportive
The coprimary end points were the percentage secondary end-point analyses were not controlled
change in body weight from baseline to week 68 for multiple comparisons and should not be
and achievement of a reduction in body weight used to infer definitive treatment effects.
of 5% or more from baseline to week 68. Con- Two estimands — the treatment policy esti-
firmatory secondary end points (in hierarchical mand (traditional intention-to-treat analysis, with
testing order) were achievement of a reduction in effects assessed regardless of treatment discontin-
body weight of 10% or more and 15% or more uation or rescue intervention) and the trial product
by week 68 and the change from baseline to estimand (effects assessed if the drug or placebo
week 68 in waist circumference, systolic blood was taken as intended) — were used to assess
pressure, physical functioning score on the 36-item treatment efficacy from different perspectives and
Short Form Health Survey (SF-36), version 2, and accounted for intercurrent events and missing data
physical function score on the Impact of Weight differently, as described previously.16 All analyses
on Quality of Life–Lite Clinical Trials Version in the statistical hierarchy were based on the pri-
(IWQOL-Lite-CT) questionnaire. (Assessments re- mary treatment policy estimand (details on analy-
lated to end points, along with supportive sec- sis methods are provided in the Supplementary
ondary and exploratory end points and safety Appendix). All reported results are for the treat-
assessments, are described in the Supplementary ment policy estimand, unless stated otherwise.
Appendix.) Body composition (total fat, total lean
body mass, and regional [abdominal] visceral fat R e sult s
mass) was measured in the DXA subpopulation
as a supportive secondary end point. Safety as- Study Participants
sessments included the number of adverse events From June through November 2018, a total of
occurring during the on-treatment period (the 1961 participants were randomly assigned to re-
time during which participants received any dose ceive semaglutide (1306 participants) or placebo
of semaglutide or placebo within the previous (655 participants). Overall, 94.3% of the partici-
49 days, with any period of temporary interrup- pants completed the trial, 91.2% had a body-
tion of the regimen excluded) and serious adverse weight assessment at week 68, and 81.1% ad-
events occurring between baseline and week 75. hered to treatment (Fig. S2). Rescue interventions
An independent external event adjudication com- were received by 7 participants in the semaglutide
mittee reviewed selected adverse events (cardio- group (2 had bariatric surgery and 5 received other
vascular events and acute pancreatitis) and deaths. antiobesity medication) and by 13 in the placebo
All standard assays were performed in a central group (3 had bariatric surgery and 10 received
laboratory. other antiobesity medication).

Table 1. Demographic and Clinical Characteristics of the Participants at Baseline.*
Semaglutide Placebo
Characteristic (N = 1306) (N = 655)
Age — yr 46±13 47±12
Female sex — no. (%) 955 (73.1) 498 (76.0)
Race or ethnic group — no. (%)†
White 973 (74.5) 499 (76.2)
Asian 181 (13.9) 80 (12.2)
Black or African American 72 (5.5) 39 (6.0)
Other 80 (6.1) 37 (5.6)
Hispanic or Latino ethnic group — no. (%)† 150 (11.5) 86 (13.1)
Body weight — kg 105.4±22.1 105.2±21.5
Body-mass index‡
Mean 37.8±6.7 38.0±6.5
Distribution — no. (%)
<30 81 (6.2) 36 (5.5)
≥30 to <35 436 (33.4) 207 (31.6)
≥35 to <40 406 (31.1) 208 (31.8)
≥40 383 (29.3) 204 (31.1)
Waist circumference — cm 114.6±14.8 114.8±14.4
Glycated hemoglobin — % 5.7±0.3 5.7±0.3
Prediabetes — no. (%)§ 593 (45.4) 263 (40.2)
Blood pressure — mm Hg
Systolic 126±14 127±14
Diastolic 80±10 80±10
Pulse — beats/min 72±10 72±10
Lipid levels — geometric mean mg/dl (coefficient of variation)¶
Total cholesterol 189.6 (20.5) 192.1 (19.4)
HDL cholesterol 49.4 (25.6) 49.5 (25.0)
LDL cholesterol 110.3 (31.6) 112.5 (29.8)
VLDL cholesterol 24.5 (45.8) 24.9 (46.5)
Free fatty acids 12.3 (57.9) 12.7 (53.8)
Triglycerides 126.2 (47.4) 127.9 (49.0)
Estimated glomerular filtration rate — geometric mean 96.3 (18.7) 95.9 (18.3)
ml/min/1.73 m2 (coefficient of variation)∥
Coexisting conditions at the time of screening**
Dyslipidemia — no. (%) 499 (38.2) 226 (34.5)
Hypertension — no. (%) 472 (36.1) 234 (35.7)
Knee osteoarthritis — no. (%) 173 (13.2) 102 (15.6)
Obstructive sleep apnea — no. (%) 159 (12.2) 71 (10.8)
Asthma or chronic obstructive pulmonary disease — no. (%) 147 (11.3) 80 (12.2)
Nonalcoholic fatty liver disease — no. (%) 101 (7.7) 62 (9.5)
Polycystic ovarian syndrome — no./total no. (%)†† 62/955 (6.5) 34/498 (6.8)
Coronary artery disease — no. (%) 32 (2.5) 17 (2.6)

Table 1. (Continued.)
Semaglutide Placebo
Characteristic (N = 1306) (N = 655)
No. of coexisting conditions at screening – no. (%)**
None 328 (25.1) 163 (24.9)
1 337 (25.8) 187 (28.5)
2 298 (22.8) 135 (20.6)
3 183 (14.0) 96 (14.7)
4 96 (7.4) 43 (6.6)
≥5 64 (4.9) 31 (4.7)
SF-36‡‡
Physical functioning score 51.0±6.9 50.8±7.9
Physical component summary score 51.1±7.3 51.1±7.9
Mental component summary score 55.4±5.7 55.5±5.9
IWQOL-Lite-CT§§
Physical function score 65.4±24.0 64.0±24.4
Total score 63.6±21.2 63.3±20.9
* Plus–minus values are means ±SD. HDL denotes high-density lipoprotein, LDL low-density lipoprotein, and VLDL
very-low-density lipoprotein.
† Race and ethnic group were reported by the investigator. The category of “other” includes Native American, Hawaiian
or other Pacific Islander, any other ethnic group, and “not applicable,” the last of which is the way race or ethnic
group was recorded in France.
‡ The body-mass index is the weight in kilograms divided by the square of the height in meters.
§ The presence of prediabetes was determined by investigators on the basis of available information (e.g., medical re-
cords, concomitant medication, and blood glucose variables) and in accordance with American Diabetes Association
criteria.17
¶ Baseline lipid levels were reported for 1281 to 1301 participants per variable in the semaglutide group, and 645 to
649 participants per variable in the placebo group. The coefficient of variation is expressed as a percentage.
∥ The coefficient of variation is expressed as a percentage.
** A coexisting condition was a history of any of the following conditions, as reported at screening: dyslipidemia, hy-
pertension, coronary artery disease, cerebrovascular disease, obstructive sleep apnea, impaired glucose metabolism,
reproductive system disorders, liver disease, kidney disease, osteoarthritis, gout, or asthma or chronic obstructive
pulmonary disease.
†† Data on polycystic ovarian syndrome include only female participants.
‡‡ Scores on the 36-Item Short-Form Health Survey (SF-36) are norm-based, transformed to a scale on which the 2009
general population of the United States has a mean score of 50 and a standard deviation of 10; higher scores indicate
better quality of life. Baseline scores are reported for 1296 participants in the semaglutide group and 650 participants
in the placebo group.
§§ Baseline scores on the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT; scores range
from 0 to 100, with higher scores indicating better patient functioning) are reported for 1296 participants in the
semaglutide group and 649 participants in the placebo group.
Demographics and baseline characteristics were Change in Body Weight

similar in the two treatment groups (Table 1). In the semaglutide group, weight loss was ob-
Most participants were female (74.1%) and White served from the first postrandomization assess-
(75.1%), with a mean age of 46 years. The mean ment (week 4) onward, reaching a nadir at week
body weight was 105.3 kg, the mean BMI 37.9, 60 (Fig. 1A and 1B). For the treatment policy
and the mean waist circumference 114.7 cm; estimand (showing the effect regardless of treat-
43.7% had prediabetes. At screening, most partici- ment discontinuation or rescue intervention), the
pants (75.0%) had at least one coexisting condi- estimated mean weight change at week 68 was
tion. The baseline characteristics of the DXA sub- −14.9% with 2.4-mg semaglutide, as compared
population are provided in Table S1. with −2.4% with placebo (estimated treatment dif-

A Body Weight Change from Baseline by Week, Observed In-Trial Data

0
−2
Placebo
Change from Baseline (%)

−4
−6
−8
−10
−12
−14
−16 Semaglutide
−18
0 4 8 12 16 20 28 36 44 52 60 68
Weeks since Randomization
No. at Risk
Placebo 655 649 641 619 615 603 592 571 554 549 540 577
Semaglutide 1306 1290 1281 1262 1252 1248 1232 1228 1207 1203 1190 1212
B Body Weight Change from Baseline by Week, Observed On-Treatment Data

0
−2
Placebo
Change from Baseline (%)
−4
−6
−8
−10
−12
−14
−16
Semaglutide
−18
0 4 8 12 16 20 28 36 44 52 60 68
Weeks since Randomization
No. at Risk
Placebo 655 647 637 613 607 593 576 555 529 520 514 499
Semaglutide 1306 1283 1259 1225 1206 1193 1176 1166 1135 1115 1100 1059
C In-Trial Data at Wk 68 D On-Treatment Data at Wk 68

100 Semaglutide Placebo 100 92.4 Semaglutide Placebo
86.4 (N=1212) (N=577) (N=1059) (N=499)
80 80 74.8
69.1
Participants (%)
Participants (%)
60 60 54.8
50.5
40 40 33.1 34.8
31.5 32.0
20 20
12.0 11.8
4.9 5.0
1.7 2.0
0 0
≥5 ≥10 ≥15 ≥20 ≥5 ≥10 ≥15 ≥20
Percent Weight Loss Percent Weight Loss
ference, −12.4 percentage points; 95% CI, −13.4 es were −16.9% and −2.4% (estimated treatment
to −11.5; P<0.001). For the trial product esti- difference, −14.4 percentage points; 95% CI,
mand (showing the effect if the drug or placebo −15.3 to −13.5).
was taken as intended), the corresponding chang- Participants who received semaglutide were

Figure 1 (facing page). Effect of Once-Weekly Semaglutide,

Other Confirmatory and Supportive
as Compared with Placebo, on Body Weight. Secondary End Points
Panels A and B show the observed mean percentage Semaglutide was associated with greater reduc-
change from baseline in body weight over time among tions from baseline than placebo in waist circum-
participants in the full analysis population during the ference (–13.54 cm with semaglutide vs. –4.13 cm
in-trial observation period (the time from random as-
with placebo; estimated treatment difference,
signment to last contact with a trial site, regardless of
treatment discontinuation or rescue intervention) and –9.42 cm; 95% CI, –10.30 to –8.53), BMI (–5.54
during the on-treatment observation period (the time with semaglutide vs. –0.92 with placebo; estimated
during which participants received semaglutide or pla- treatment difference, –4.61; 95% CI, –4.96 to
cebo within the previous 2 weeks, with any period of –4.27), and systolic and diastolic blood pressure
temporary interruption of a regimen excluded). I bars
at week 68 (Table 2, Table S2, and Figs. S5 and
indicate standard errors. The numbers at risk are the
numbers of participants with available data contribut- S6). Benefits favoring semaglutide were also not-
ing to the means at each visit. Panels C and D show the ed with respect to changes in glycated hemoglo-
observed percentages of participants who had body- bin, fasting plasma glucose, C-reactive protein,
weight reductions of at least 5%, 10%, 15%, and 20% and fasting lipid levels (Table 2).
from baseline to week 68 during the in-trial observation
period and on-treatment observation period. Percent-
ages were based on the number of participants for
Exploratory End Points
whom data were available at the week 68 visit — 1212 Among participants with prediabetes at baseline,
participants in the semaglutide group and 577 in the semaglutide was associated with improvements
placebo group during the in-trial observation period in glycated hemoglobin levels at week 68, and
and 1059 participants in the semaglutide group and
84.1% of participants in the semaglutide group
499 in the placebo group during the on-treatment ob-
servation period. who had prediabetes at baseline, as compared with
47.8% of participants in the placebo group with
prediabetes at baseline, reverted to normogly-
more likely to lose 5% or more, 10% or more, cemia. Results for these and other selected ex-
15% or more, and 20% or more of baseline body ploratory end points are presented in Table 2 and
weight at week 68 than those who received pla- Table S3.
cebo (P<0.001 for the 5%, 10%, and 15% thresh-
olds; the 20% threshold was not part of the Physical Functioning and Other
statistical testing hierarchy) (Table 2, Fig. 1C Participant-Reported Outcomes
and 1D, and Table S2). Among the participants SF-36 physical functioning scores (with possible
for whom data were available at the week 68 visit norm-based scores ranging from 19.03 to 57.60)
(1212 participants in the semaglutide group and improved significantly more with semaglutide
577 in the placebo group), these thresholds were than with placebo at week 68 (P<0.001), and both
reached by 86.4% (1047 participants), 69.1% (838 SF-36 physical and mental component summary
participants), 50.5% (612 participants), and 32.0% scores favored semaglutide (Table 2, Table S2,
(388 participants), respectively, in the semaglutide and Fig. S7). IWQOL-Lite-CT physical function
group, as compared with 31.5% (182 participants), scores improved significantly more with sema-
12.0% (69 participants), 4.9% (28 participants), glutide than with placebo at week 68 (P<0.001)
and 1.7% (10 participants) in the placebo group (Table 2 and Table S2), and there were favorable
(Fig. 1C, with on-treatment data shown in Fig. 1D effects over placebo on IWQOL-Lite-CT total
and the cumulative distribution of change from scores. The results of SF-36 and IWQOL-Lite-CT
baseline shown in Fig. S3). The change in body assessments showed that participants were more
weight from baseline to week 68 was −15.3 kg in likely to have clinically meaningful within-per-
the semaglutide group as compared with −2.6 kg son improvements in physical functioning with
in the placebo group (estimated treatment dif- semaglutide than with placebo (Table S4).
ference, −12.7 kg; 95% CI, −13.7 to −11.7) (Fig. S4).
Data on change in body weight and achieved re- Change in Body Composition
duction in body weight of 5% or more (coprimary In the DXA subpopulation (140 participants), total
end points) as well as confirmatory and selected fat mass and regional visceral fat mass were re-
supportive secondary end points for the trial duced from baseline with semaglutide (Table S5).
product estimand are provided in Table S2. Although total lean body mass decreased in ab-

996
Table 2. Coprimary, Confirmatory, and Selected Supportive Secondary and Exploratory End Points for the Treatment Policy Estimand.*
Difference between
Semaglutide Placebo Semaglutide and Placebo
End Point (N = 1306) (N = 655) (95% CI)† Odds Ratio P Value
Coprimary end points assessed in the overall population
Percent body-weight change from baseline to wk 68 –14.85 –2.41 −12.44 (–13.37 to –11.51) <0.001
Participants with body-weight reduction ≥5% at wk 68 — %‡ 86.4 31.5 11.2 (8.9 to 14.2) <0.001
Confirmatory secondary end points assessed in the overall population
The
Change from baseline to wk 68

Waist circumference — cm –13.54 –4.13 –9.42 (–10.30 to –8.53) <0.001
Systolic blood pressure — mm Hg –6.16 –1.06 –5.10 (–6.34 to –3.87) <0.001
SF-36 physical functioning score 2.21 0.41 1.80 (1.18 to 2.42) <0.001
IWQOL-Lite-CT physical function score 14.67 5.25 9.43 (7.50 to 11.35) <0.001
n engl j med 384;11

Supportive secondary end points assessed in the overall population§
Participants with body-weight reduction ≥20% at wk 68 — %‡ 32.0 1.7 26.9 (14.2 to 51.0)
Change from baseline to wk 68
nejm.org
Body weight — kg –15.3 –2.6 –12.7 (–13.7 to –11.7)
n e w e ng l a n d j o u r na l

of
Body-mass index –5.54 –0.92 –4.61 (–4.96 to –4.27)

Glycated hemoglobin — percentage points –0.45 –0.15 –0.29 (–0.32 to –0.26)
Fasting plasma glucose — mg/dl –8.35 –0.48 –7.87 (–9.04 to –6.70)
March 18, 2021

Diastolic blood pressure — mm Hg –2.83 –0.42 –2.41 (–3.25 to –1.57)

m e dic i n e
Lipid levels, ratio of wk 68 value to baseline¶

Total cholesterol 0.97 1.00 0.97 (0.95 to 0.98)
HDL cholesterol 1.05 1.01 1.04 (1.02 to 1.05)
LDL cholesterol 0.97 1.01 0.96 (0.94 to 0.98)
VLDL cholesterol 0.78 0.93 0.84 (0.81 to 0.87)
Free fatty acids 0.83 0.93 0.89 (0.83 to 0.94)
Triglycerides 0.78 0.93 0.84 (0.81 to 0.87)
C-reactive protein, ratio of wk-68 value to baseline¶ 0.47 0.85 0.56 (0.51 to 0.61)
solute terms (kg), the proportion of lean body
‡ Denominators for the percentages of participants observed to have body-weight reduction of ≥5%, ≥10%, ≥15%, and ≥20% at week 68 are the numbers of participants for whom data
assessed treatment effect assuming all participants adhered to treatment and did not receive rescue intervention). Continuous end-point analyses were conducted with the use of the
analysis-of-covariance method, with randomized treatment as a factor and baseline end-point value as a covariate and a multiple imputation approach for missing data.15 Analyses of
* The treatment policy estimand assesses treatment effect regardless of treatment discontinuation or rescue intervention; see Table S2 for corresponding data for the estimand (which
† The difference is the estimated difference between the groups except in the case of lipid and C-reactive protein levels, for which the comparison is the ratio of values for semaglutide
mass relative to total body mass increased with
P Value
semaglutide.
Safety and Side-Effect Profile

Similar percentages of participants in the sema-
glutide and placebo groups reported adverse events
Odds Ratio
(89.7% and 86.4%, respectively) (Table 3). Gastro-

intestinal disorders (typically nausea, diarrhea,
§ Supportive secondary and exploratory end point analyses were not adjusted for multiplicity, and P values are therefore not reported for these end points.
∥ The exploratory end point in the prediabetes subpopulation was assessed in 593 participants in the semaglutide group and in 263 in the placebo group.
vomiting, and constipation) were the most fre-
quently reported events and occurred in more
participants receiving semaglutide than those
receiving placebo (74.2% vs. 47.9%). Most gastro-
Semaglutide and Placebo
–0.34 (–0.39 to –0.29)

Difference between
intestinal events were mild-to-moderate in sever-

ity, were transient, and resolved without perma-
(95% CI)†
nent discontinuation of the regimen (Fig. S8).

Serious adverse events were reported in 9.8%
were available at the week 68 visit — 1212 participants in the semaglutide group and 577 participants in the placebo group.
and 6.4% of semaglutide and placebo partici-

pants, respectively (Table 3), with the difference
due primarily to a difference between the groups
in the incidence of serious gastrointestinal dis-
categorical end points were conducted with the use of logistic regression, with the same factor and covariate.
orders (1.4% of participants in the semaglutide

(N = 655)
Placebo
–0.17
47.8
group and 0% in the placebo group) and hepa-

tobiliary disorders (1.3% with semaglutide and
0.2% with placebo). More participants in the
semaglutide group than in the placebo group
¶ Ratios to baseline and corresponding baseline values were log-transformed before analysis.
(7.0% vs. 3.1%) discontinued treatment owing to

Semaglutide
(N = 1306)
** The percentage-point change in glycated hemoglobin was not a prespecified end point.
adverse events (mainly gastrointestinal events)

–0.52
84.1
(Table 3 and Fig. S9). One death was reported in

each group, with neither considered by the inde-
pendent external event adjudication committee
to be related to receipt of semaglutide or placebo
Change in glycated hemoglobin level from baseline to wk 68 — per-
(Table 3).
Gallbladder-related disorders (mostly choleli-
Exploratory end-point assessed in the prediabetes subpopulation§∥
thiasis) were reported in 2.6% and 1.2% of par-

ticipants in the semaglutide and placebo groups,
respectively. Mild acute pancreatitis (according
Participants with normoglycemia at wk 68 — (%)
to the Atlanta classification18) was reported in

three participants in the semaglutide group (one
participant had a history of acute pancreatitis,
and the other two participants had both gall-
stones and pancreatitis); all recovered during the
trial period. There was no difference between
groups in the incidence of benign and malignant
neoplasms. Additional safety variables are de-
centage points**
scribed in Table 3 and Table S6.

to those for placebo.
Discussion
End Point
In this trial, we found that adults with obesity

(or overweight with one or more weight-related
coexisting conditions) and without diabetes had

Table 3. Adverse Events.*
Semaglutide Placebo
Adverse Event (N = 1306) (N = 655)
No. of No. of Events/100 No. of No. of Events/100

participants (%) events person-yr participants (%) events person-yr
Any adverse event 1171 (89.7) 9658 566.1 566 (86.4) 3302 398.0
Serious adverse events 128 (9.8) 164 9.6 42 (6.4) 53 6.4
Adverse events leading to discontinuation 92 (7.0) 123 7.2 20 (3.1) 23 2.8
of drug or placebo
Gastrointestinal disorders 59 (4.5) 78 4.6 5 (0.8) 5 0.6
Fatal events†‡ 1 (0.1) 1 0.1 1 (0.2) 3 0.3
Adverse events reported in ≥10% of
participants§
Nausea 577 (44.2) 1068 62.6 114 (17.4) 146 17.6
Diarrhea 412 (31.5) 766 44.9 104 (15.9) 138 16.6
Vomiting 324 (24.8) 636 37.3 43 (6.6) 52 6.3
Constipation 306 (23.4) 390 22.9 62 (9.5) 73 8.8
Nasopharyngitis 281 (21.5) 480 28.1 133 (20.3) 216 26.0
Headache 198 (15.2) 387 22.7 80 (12.2) 104 12.5
Dyspepsia 135 (10.3) 179 10.5 23 (3.5) 30 3.6
Abdominal pain 130 (10.0) 175 10.3 36 (5.5) 41 4.9
Upper respiratory tract infection 114 (8.7) 158 9.3 80 (12.2) 116 14.0
Safety focus areas¶
Gastrointestinal disorders∥ 969 (74.2) 4309 252.6 314 (47.9) 739 89.1
Gallbladder-related disorders 34 (2.6) 42 2.5 8 (1.2) 8 1.0
Hepatobiliary disorders∥ 33 (2.5) 40 2.3 5 (0.8) 5 0.6
Cholelithiasis 23 (1.8) 24 1.4 4 (0.6) 4 0.5
Hepatic disorders 31 (2.4) 37 2.2 20 (3.1) 24 2.9
Acute pancreatitis** 3 (0.2) 3 0.2 0 — —
Cardiovascular disorders† 107 (8.2) 134 7.2 75 (11.5) 96 10.5
Allergic reactions 96 (7.4) 108 6.3 54 (8.2) 63 7.6
Injection-site reactions 65 (5.0) 99 5.8 44 (6.7) 82 9.9
Malignant neoplasms† 14 (1.1) 14 0.8 7 (1.1) 7 0.8
Psychiatric disorders∥ 124 (9.5) 160 9.4 83 (12.7) 113 13.6
Acute renal failure 3 (0.2) 4 0.2 2 (0.3) 2 0.2
Hypoglycemia 8 (0.6) 15 0.9 5 (0.8) 7 0.8
* Adverse events are shown for the safety analysis population (all randomly assigned participants exposed to at least one dose of trial drug or
placebo); since all participants received at least one dose of drug or placebo, the safety population is the same as the full-analysis population.
Included are all adverse events that occurred during the on-treatment period (i.e., the period during which any dose of semaglutide or pla-
cebo was administered within the previous 49 days, with any period of temporary interruption of a regimen excluded), unless indicated oth-
erwise. Adverse events were classified by severity as mild (causing minimal discomfort and not interfering with everyday activities), moderate
(causing sufficient discomfort to interfere with normal everyday activities), or severe (preventing normal everyday activities).
† Included are events that were observed during the in-trial period (the time from random assignment to last contact with a trial site, re-
gardless of treatment discontinuation or rescue intervention).
‡ In the semaglutide group, sudden cardiac death occurred in one participant with a medical history of hypertension and obstructive sleep
apnea who had discontinued semaglutide. In the placebo group, death due to glioblastoma, aspiration pneumonia, and severe sepsis oc-
curred in one participant each who had discontinued placebo.
§ Shown are the most common adverse events, according to the preferred term in the Medical Dictionary for Regulatory Activities
(MedDRA), version 22.1, reported in 10% or more of participants in either treatment group.
¶ On the basis of therapeutic experience with glucagon-like peptide-1 receptor agonists and regulatory feedback and requirements, a num-
ber of safety focus areas were prespecified as being of special interest in the safety evaluation. Identified through searches of MedDRA,
these preferred terms were judged to be relevant for each of the safety focus areas.
∥ This is a system organ class. (For gallbladder-related disorders, hepatobiliary disorders is the system organ class and cholelithiasis is the
preferred term.)
** Acute pancreatitis was confirmed by the event adjudication committee.

a mean weight loss of 14.9% from baseline with with type 2 diabetes.33 The weight loss and im-
semaglutide as an adjunct to lifestyle interven- provements with respect to cardiometabolic risk
tion. This loss exceeded that with placebo plus factors with semaglutide reported here will be
lifestyle intervention by 12.4 percentage points. complemented by an ongoing cardiovascular
The 14.9% mean weight loss that we observed in outcomes trial in participants with overweight
the semaglutide group is substantially greater or obesity and established cardiovascular disease
than the weight loss of 4.0 to 10.9% from base- (the SELECT trial; ClinicalTrials.gov number,
line with approved antiobesity medications.3,19 NCT03574597).
Moreover, 86% of participants who received Liraglutide administered subcutaneously once
semaglutide, as compared with 32% of those who daily is the only GLP-1 receptor agonist approved
received placebo, lost 5% or more of baseline for weight management.3,19,34 Our trial showed
body weight, a widely used criterion of clinically greater mean placebo-corrected weight reductions
meaningful response.2,3,20,21 Weight loss with sema- with once-weekly 2.4-mg semaglutide plus life-
glutide stems from a reduction in energy intake style intervention (12.4%) than those reported with
owing to decreased appetite, which is thought to once-daily 3.0-mg liraglutide plus lifestyle in-
result from direct and indirect effects on the tervention in the 56-week SCALE (Satiety and
brain.22-25 Weight loss with semaglutide was ac- Clinical Adiposity — Liraglutide Evidence in Non-
companied by greater improvements than placebo diabetic and Diabetic Individuals Obesity and Pre-
with respect to cardiometabolic risk factors, in- diabetes) trial (4.5%).34,35 In addition, the weight-
cluding reductions in waist circumference, blood loss phase with semaglutide persisted longer than
pressure, glycated hemoglobin levels, and lipid that reported with liraglutide35 and did not reach
levels; a greater decrease from baseline in C-reac- the nadir until week 60. However, these two stud-
tive protein, a marker of inflammation; and a ies differed in their participant population, which
greater proportion of participants with normo- limits the robustness of between-study com-
glycemia. Semaglutide also improved physical parisons.
functioning, as assessed by SF-36 and IWQOL- At week 68, 31% of participants who received
Lite-CT, a finding that is notable given that over- placebo had lost at least 5% of baseline body
weight and obesity significantly impair health- weight, with 12% and 5% having achieved reduc-
related quality of life.26 Statistical superiority of tions of at least 10% and at least 15%, respectively,
semaglutide over placebo was achieved for all findings that show good adherence to lifestyle
end points in the hierarchical testing procedure. interventions. Similar results were observed at
Weight loss of 10 to 15% (or more) is recom- week 56 in the SCALE Obesity and Prediabetes
mended in people with many complications of trial.35
overweight and obesity (e.g., prediabetes, hyper- Currently, approved antiobesity drugs require
tension, and obstructive sleep apnea).1,20,21,27 In administration once, twice, or three times daily,3,19
the semaglutide group, approximately 70% of and a once-weekly regimen may improve treat-
participants achieved a weight loss of at least 10%, ment adherence. The once-weekly 2.4-mg dose of
and approximately 50% achieved a weight loss of semaglutide was chosen for the present study on
at least 15%. Furthermore, one third of partici- the basis of pharmacokinetic modeling that sug-
pants treated with semaglutide lost at least 20% gested that the 2.4-mg weekly dose had a maxi-
of baseline weight, a reduction approaching that mum steady-state concentration similar to a
reported 1 to 3 years after bariatric surgery, par- once-daily 0.4-mg dose investigated in a phase
ticularly sleeve gastrectomy (approximately 20 to 2 dose-finding trial in participants with obesi-
30% weight loss).28-31 The magnitude of reduc- ty.14 The results of our study with once-weekly
tion in cardiometabolic risk is assumed to be pro- semaglutide at a 2.4-mg dose are consistent with
portional to the amount of weight lost with both the results of the phase 2 study, which showed
approaches (i.e., pharmacotherapy or surgery).32 an 11.6% greater reduction in body weight with
Analyses from the DXA substudy suggested once-daily semaglutide at a dose of 0.4 mg than
that semaglutide led to greater reduction in fat with placebo after 52 weeks of treatment.14
mass than lean body mass, a finding consistent The safety of semaglutide was consistent with
with previous findings with semaglutide (at a dose that reported in the phase 2 study with once-
of 1.0 mg) in persons with obesity22 and in those daily dosing in participants with obesity14 and in

the trials of once-weekly subcutaneous semaglu- fees, and fees for serving as an investigator, all paid to Univer-
sity of Liverpool, and lecture fees from Novo Nordisk, and advi-
tide in persons with type 2 diabetes (involving sory board fees from Takeda Medical Research Foundation; Dr.
more than 8000 participants receiving doses up Batterham, receiving consulting fees from Boehringer Ingel-
to 1 mg),12 as well as with that reported for the heim, Pfizer, and ViiV Healthcare and consulting fees and lec-
ture fees from Novo Nordisk; Dr. Calanna, being employed by
GLP-1 receptor agonist class in general.13,36 As is Novo Nordisk; Dr. Davies, receiving grant support from Astra-
typical of this drug class,13,37 transient, mild-to- Zeneca, lecture fees from AstraZeneca Pharma India, advisory
moderate gastrointestinal disorders were the most board fees from BI-LLY Alliance, Lexicon Pharmaceuticals, and
Sanofi, advisory board fees and lecture fees from Boehringer
frequently reported adverse events, and more par- Ingelheim and Eli Lilly, lecture fees from Boehringer Ingelheim
ticipants in the semaglutide group than in the (China), Boehringer Ingelheim (Philippines), Boehringer Ingel-
placebo group discontinued the assigned regimen heim Saudi Arabia Trading, Boehringer Ingelheim (Poland),
Napp Pharmaceuticals, Sanofi Romania, and Sanofi (Japan),
after such events. Nausea was the most common advisory board fees and lecture fees from Boehringer Ingelheim
gastrointestinal event, occurring primarily during International, and grant support, lecture fees, and advisory
the dose-escalation period, a finding similar to board fees from Novo Nordisk; Dr. Van Gaal, receiving lecture
fees from AstraZeneca and Boehringer Ingelheim and advisory
that reported with liraglutide at a dose of 3.0 mg.35 board fees and lecture fees from Merck and Novo Nordisk; Dr.
Gallbladder-related disorders, principally chole- Lingvay, receiving advisory board fees and consulting fees from
lithiasis, were more common in the semaglutide AstraZeneca, consulting fees from Bayer HealthCare Pharma-
ceuticals, Eli Lilly, Intarcia, Intercept Pharmaceuticals, Janssen
group, a finding consistent with previous re- Global Services, MannKind, Target Pharma, Valeritas, and Zealand
ports for GLP-1 receptor agonists38,39 and with Pharma, advisory board fees from Boehringer Ingelheim and
the known effects of rapid weight loss.40,41 The Sanofi US Services, grant support, paid to UT Southwestern,
from Merck, grant support, paid to his institution, from Mylan
incidence of cholelithiasis with semaglutide was Pharmaceuticals and Pfizer, and grant support, paid to UT South-
in line with that of liraglutide at a dose of 3.0 mg.35 western, advisory board fees, consulting fees, and travel support
No new safety concerns arose. from Novo Nordisk; Dr. McGowan, receiving educational fees
from AstraZeneca, Merck, and Orexigen Therapeutics, lecture
Strengths of this trial included the large sam- fees from Janssen Biotech, advisory board fees from Johnson &
ple size and high rates of adherence to the treat- Johnson Health Care Systems, grant support, paid to Guys and
ment regimen and completion of the trial. Limi- St. Thomas’ Hospital, consulting fees, and educational fees
from Novo Nordisk, and owning stock in Reset Health Clinics;
tations included the preponderance of women Dr. Rosenstock, receiving grant support, advisory board fees, and
and White participants, the relatively short dura- travel support from Applied Therapeutics, Intarcia, and Oramed,
tion of the trial, the exclusion of persons with grant support and consulting fees from AstraZeneca, grant sup-
port, advisory board fees, lecture fees, and travel support from
type 2 diabetes, and the potential that partici- Boehringer Ingelheim, Novo Nordisk, and Sanofi US Services,
pants who were enrolled may represent a sub- grant support and advisory board fees from Eli Lilly, grant sup-
group with greater commitment to weight-loss port from Genentech, GlaxoSmithKline, Janssen Biotech, Lexicon
Pharmaceuticals, Novartis, Pfizer, and REMD Biotherapeutics,
efforts than the general population. Although and advisory board fees from Zealand Pharma; Dr. Tran, being
the DXA data we report provide greater insight employed by and owning stock in Novo Nordisk; Dr. Wadden,
into the weight-loss effects of semaglutide, such receiving grant support, paid to the University of Pennsylvania,
and advisory board fees from Novo Nordisk and advisory board
assessments were performed in only a subpopu- fees from WW International; Dr. Wharton, receiving lecture fees
lation of participants. from AstraZeneca and Bausch and Lomb and grant support,
Our trial showed that among adults with lecture fees, and advisory board fees from Novo Nordisk; Dr.
Yokote, receiving lecture fees from Amgen, Janssen Pharmaceu-
overweight or obesity (without diabetes), once- ticals, Kyowa Hakko Kirin, Novartis Pharma, and Sanofi, grant
weekly subcutaneous semaglutide plus lifestyle support and lecture fees from Astellas Pharma, Daiichi Sankyo,
intervention was associated with substantial, Eli Lilly Japan, Merck Sharp and Dohme, Mitsubishi Tanabe
Pharma, Nippon Boehringer Ingelheim, Novo Nordisk, Ono
sustained, clinically relevant mean weight loss of Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Taisho
14.9%, with 86% of participants attaining at Toyama Pharmaceutical, and Takeda Pharmaceutical, advisory
least 5% weight loss. board fees and lecture fees from AstraZeneca, grant support,
lecture fees, and advisory board fees from Kowa Company and
Supported by Novo Nordisk. Novo Nordisk, and lecture fees and advisory board fees from
Dr. Wilding reports receiving advisory board fees, paid to his Sanofi; Mr. Zeuthen, being employed by and owning stock in
institution, from Astellas Pharma, grant support and fees for Novo Nordisk; and Dr. Kushner, receiving advisory board fees
membership on a data and safety monitoring board, both paid from Novo Nordisk and Weight Watchers. No other potential
to University of Liverpool, lecture fees, and travel support from conflict of interest relevant to this article was reported.
AstraZeneca, advisory board fees, paid to his institution, and Disclosure forms provided by the authors are available with
lecture fees from Boehringer Ingelheim, Napp, and Sanofi Pas- the full text of this article at NEJM.org.
teur, advisory board fees, paid to his institution, from Eli Lilly, A data sharing statement provided by the authors is available
Janssen Global Services, Rhythm, and Wilmington Healthcare, with the full text of this article at NEJM.org.
lecture fees from Mundipharma, grant support, advisory board We thank the trial participants and the trial site staff; Lisa

von Huth Smith of Novo Nordisk, Denmark, for support with Axis, a division of Spirit Medical Communications Group, for
data presentation of participant-reported outcomes and critical medical writing and editorial assistance with an earlier draft of
review of an earlier draft of the manuscript; and Paul Barlass of the manuscript (funded by Novo Nordisk).
Appendix
The authors’ affiliations are as follows: the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical
Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine,
University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre
for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and
Endocrinology, Guy’s and St. Thomas’ NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of
Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester — all in the United Kingdom; Novo Nordisk,
Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital,
University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data
Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) — both
in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York Univer-
sity, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology,
and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba
University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University,
Chicago (R.F.K.).
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Once-Weekly Semaglutide in Adults with Overweight

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The New England Journal of Medicine

maintenance dose of 2.4 mg weekly by week 16 Statistical Analysis

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Table 1. Demographic and Clinical Characteristics of the Participants at Baseline.*

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Demographics and baseline characteristics were Change in Body Weight

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A Body Weight Change from Baseline by Week, Observed In-Trial Data

Change from Baseline (%)

B Body Weight Change from Baseline by Week, Observed On-Treatment Data

C In-Trial Data at Wk 68 D On-Treatment Data at Wk 68

Percent Weight Loss Percent Weight Loss

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The New England Journal of Medicine

Figure 1 (facing page). Effect of Once-Weekly Semaglutide,

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Change from baseline to wk 68

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Body-mass index –5.54 –0.92 –4.61 (–4.96 to –4.27)

March 18, 2021

Copyright © 2021 Massachusetts Medical Society. All rights reserved.

Lipid levels, ratio of wk 68 value to baseline¶

solute terms (kg), the proportion of lean body

Safety and Side-Effect Profile

(89.7% and 86.4%, respectively) (Table 3). Gastro-

–0.34 (–0.39 to –0.29)

intestinal events were mild-to-moderate in sever-

nent discontinuation of the regimen (Fig. S8).

and 6.4% of semaglutide and placebo partici-

orders (1.4% of participants in the semaglutide

group and 0% in the placebo group) and hepa-

(7.0% vs. 3.1%) discontinued treatment owing to

adverse events (mainly gastrointestinal events)

(Table 3 and Fig. S9). One death was reported in

thiasis) were reported in 2.6% and 1.2% of par-

to the Atlanta classification18) was reported in

scribed in Table 3 and Table S6.

In this trial, we found that adults with obesity

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Table 3. Adverse Events.*

No. of No. of Events/100 No. of No. of Events/100

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TRACK THIS ARTICLE’S IMPACT AND REACH

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