Review Article

Journal of the
ASEAN Federation of
Endocrine Societies

Efficacy and Safety of Semaglutide for Weight Loss in

Obesity Without Diabetes: A Systematic Review and Meta-Analysis*
Hanna Clementine Tan,1 Oliver Allan Dampil,2 Maricar Mae Marquez1

Department of Medicine, St. Luke’s Medical Center, Quezon City, Philippines

1

2
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, St. Luke’s Medical Center, Quezon City, Philippines

Abstract

Background. The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility
in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of
subcutaneous semaglutide as treatment for obesity in patients without diabetes.

Methodology. A comprehensive search of PubMed/MEDLINE, Cochrane and Google scholar was performed to identify
trials on the efficacy and safety of subcutaneous semaglutide on patients with obesity without diabetes. Primary outcome
was expressed as percent mean weight difference. Secondary outcomes including risk for gastrointestinal adverse
events, discontinuation of treatment and serious adverse events were expressed as risk ratios. These were calculated
using the random effects model.

Results. The study included 4 randomized controlled trials having a total of 3,613 individuals with obesity without
diabetes. The mean difference for weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI)
(-12.81,-10.90), p<0.00001]. Secondary outcomes showed that the risk of developing gastrointestinal adverse events
was 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], p<0.00001). Risk for discontinuation due
to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], p=0.001) and the risk for
serious adverse events was 1.6 times more likely for semaglutide (RR1.60, 95%CI [1.24, 2.07], p=0.0003). Serious
events were mostly of gastrointestinal and hepatobiliary disorders such as acute pancreatitis and cholelithiasis.

Conclusion. Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight
loss with an 11.85% reduction from baseline compared to placebo. This supports the use of semaglutide for weight
management in obesity. However, risk of gastrointestinal adverse events, discontinuation of treatment and serious
adverse events were higher in the semaglutide group versus placebo.

Key words: obesity, Glucagon-like Peptide -1, weight loss, semaglutide

INTRODUCTION Liraglutide, a glucagon-like peptide-1 receptor agonist

(GLP1-RA), has been approved for the pharmacologic
Obesity is a chronic relapsing condition,1 defined as treatment of obesity, and is the only drug in its class
excessive fat accumulation2 with serious clinical compli- approved for this indication.6,7 GLP-1 RAs were developed
cations such as diabetes mellitus, cardiovascular disease, for the treatment of diabetes since the incretin GLP-
musculoskeletal disorders and malignancy.2,3 It is caused 1 was shown to decrease blood glucose by stimulating
by an imbalance between energy intake and expenditure.4 insulin secretion and decreasing glucagon release. It also
Obesity has tripled worldwide since 1975. In 2016, more promotes weight loss by inducing satiety, leading to
than 1.9 billion adults older than 18 years were over- decreased caloric intake by delaying gastric emptying. In
weight and 650 million were obese.2 Treatment options the brain, it decreases appetite through the stimulation
for obesity include bariatric surgery and nonsurgical of satiety centers indirectly through neural afferents and
treatment such as diet modification, behavioral therapy directly by crossing the blood brain barrier.4 GLP-1 RAs
and pharmacologic therapy.5 available in the market have different duration of action,
frequency of administration and dosing.8 Dosing frequency

________________________________________

ISSN 0857-1074 (Print) | eISSN 2308-118x (Online) Corresponding author: Hanna Clementine Q. Tan, MD
Printed in the Philippines Department of Medicine, St. Luke’s Medical Center,
Copyright © 2022 by Tan et al. 279 E. Rodriguez Sr. Ave., Quezon City, 1112 Philippines
Received: March 2, 2022. Accepted: June 2, 2022. Tel. No.: +632-8723-0101
Published online first: August 23, 2022. E-mail: tanhanna7@gmail.com
https://doi.org/10.15605/jafes.037.02.14 ORCiD: https://orcid.org/0000-0002-3883-8197

* Presented in the poster exhibition category of the 9th Seoul International Congress of Endocrinology and Metabolism (SICEM 2021), awarded Best Poster Exhibition Award.

Vol. 37 No. 2 November 2022 www.asean-endocrinejournal.org 65

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
66 Hanna Clementine Tan, et al Semaglutide for Weight Loss in Obesity Without Diabetes

affects adherence to therapy and studies show that a once without T2DM. The search strategy was “semaglutide”
weekly dosing was associated with significantly better AND “obesity.” No filter was used. Ongoing trials were
adherence.9,10 GLP-1 RAs available for once weekly dosing also sought in the relevant search. Two reviewers (HCT and
are exenatide, and the larger molecular weight dulaglutide MMM) independently searched the databases to identify
and albiglutide. In a head-to-head review of GLP-1 RAs, all potentially eligible studies and reviewed the full articles
albiglutide and dulaglutide were associated with less for inclusion. Selected articles were then compared and
weight loss.11 Large molecular weight GLP-1 RAs do not the decision to include the article was reached through a
cross the blood brain barrier, which decreases its effect on consensus. Consult with the third author (OAD) was done
stimulating the satiety center and leads to lesser weight loss when a consensus could not be made.
compared with GLP-1 RAs with smaller molecular weight.12
Semaglutide is a once weekly GLP-1 RA with smaller Types of studies and patient characteristics
molecular weight12 that is currently used for the treatment
of type 2 diabetes mellitus (T2DM) and is associated with RCTs were included in this review. Only published studies
dose dependent reduction in glycosylated hemoglobin on adults with a BMI of ≥30 kg/m2 or ≥27 kg/m2 with
(HbA1c) as well as body weight in patients with diabetes.6 at least one weight-related comorbidity were included.
It has not been approved for the treatment of obesity but Patients with diabetes mellitus were excluded. The inclusion
the research study comparing a semaglutide to liraglutide and exclusion criteria of each article were reviewed to
in type 2 diabetics (SUSTAIN 10 trial) has shown that it confirm the target population.
was superior to liraglutide for weight reduction.13
Interventions/outcome
Only a few drugs have been approved for treatment of
obesity.6,7 Some of these drugs include phentermine, Studies that measured percent weight loss from baseline
bupropion/naltrexone and phentermine/topiramate. Safety after treatment with semaglutide were included. Studies
has been a major concern since these drugs cause adverse that compared semaglutide with medications other than
psychological and physical effects.7 It is therefore necessary GLP-1 RA or placebo were excluded.
to have an overall efficacy and safety evaluation of
semaglutide as a promising option for the pharmaco- Selection of studies
logic treatment of obesity. We conducted this systematic
review and meta-analysis to present a comprehensive Two authors (HCT, MMM) independently screened and
picture of the efficacy and safety of semaglutide for weight reviewed the abstracts and articles for inclusion. Articles
loss in obesity without diabetes. were selected based on the inclusion criteria and decision
to include the article was made through consensus.
Research question After removal of duplicates, the search yielded 945
publications. Based on title and abstract, 895 were either
Among individuals with obesity without T2DM, how a clinical trial, review, meta-analysis, or cohort study and
effective and safe is semaglutide for weight loss? these were excluded. Full texts of 50 studies were reviewed
and 4 were eligible for systematic review. Studies that had
Objectives comparison groups and outcome not compatible with
the goals of this review were excluded.
The objective of the study was to conduct a systematic
review and meta-analysis on randomized controlled trials Data extraction and risk of bias assessment
(RCT) of subcutaneous semaglutide on patients who are
obese without T2DM. It aimed to determine the percent Selected articles were downloaded and independently
weight reduction from baseline after treatment with reviewed by the reviewers. Discrepancies in the selection
semaglutide. The study also aimed to determine the risk of process were resolved through discussion and reaching a
gastrointestinal adverse events, risk for discontinuation and consensus. Consultation with a third expert investigator
serious adverse events after treatment with semaglutide. was done when a consensus could not be reached. A
data collection form was created and was used to extract
METHODOLOGY information from each article. This included author,
demographics of study population, inclusion and exclusion
Search strategy criteria, intervention and comparison methods, primary
outcome of percent weight reduction and gastrointestinal
This meta-analysis was performed in accordance to the adverse events. Quality assessment was done using
PRISMA 2020 statement. A comprehensive systematic the Cochrane Collaboration’s tool for assessing risk of
search of PubMed/MEDLINE, Cochrane and Google bias. Each article was critically appraised for risk of bias,
scholar was performed from inception to June 2021 to which includes random sequence generation, allocation
identify publications in the English or foreign language concealment, blinding of participants and personnel,
with adequate English translations on semaglutide versus blinding of outcome assessment, incomplete outcome data,
placebo and other GLP-1 RAs for weight loss in obesity selective reporting, and other bias. These were graded

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Semaglutide for Weight Loss in Obesity Without Diabetes Hanna Clementine Tan, et al 67

as high, low, or unclear, and discrepancies were settled 945 publications from
through constructive discussion and reaching a consensus. database search after
removal of duplicates

Data synthesis and analysis

945 titles and 895 excluded based on title
abstracts screened and abstract alone
Data synthesis and analysis were performed using Revman
19 in a foreign language, inaccessible
5.4 for Mac. The effect measure was reported as percent
mean weight change at 95% confidence interval. A p value
< 0.05 was considered as statistically significant. Statistical 50 full-texts assessed 46 records excluded:
for eligibility • 45 done in patients with diabetes
heterogeneity between trials were assessed using the I2 • 12 used different intervention
statistics. An I2 value of 30 to 60% indicated moderate • 8 different outcomes
4 articles included • 1 not in obese population
heterogeneity, 50 to 90% substantial heterogeneity, and
in meta-analysis
75 to 100% indicated considerable heterogeneity. Random
effects model was used when heterogeneity was identified. Figure 1. Flow diagram for systematic review and study
When significant heterogeneity was detected even selection of randomized controlled trials on semaglutide for
after using random effects model, a sensitivity analysis weight loss in patients who are obese without diabetes.
was performed. This was done by repeating the initial
analysis, reviewing the inclusion and exclusion criteria
and evaluating the methodology of each trial to see what
could have contributed to the heterogeneity.

Registration

This study was registered with Prospero with ID

CRD42021251299.

RESULTS

Study selection

The search yielded 1208 articles, of which 263 were

duplicates. After removal of duplicates and 895 articles
based on title and abstract alone, 50 full text articles were
assessed for eligibility, of which 46 were excluded since
the studies were either done in patients with diabetes or
non-obese population, used an intervention other than
semaglutide, or had an outcome that was not compatible
with the goals of this review. After careful evaluation,
4 RTCs were included in the review (Figure 1). These
Figure 2. Risk of bias assessment of the included
trials measured the percent change in body weight after
randomized controlled trials.
treatment with semaglutide versus placebo and reported
the most common adverse effects associated with treatment.
No ongoing similar studies were identified in the search. studies where participants were randomized to receive
semaglutide or placebo at the start of study, Rubino’s
Study characteristics study randomized participants after the target dose was
reached to continue with semaglutide or switch to matching
Across 4 trials, 3,613 individuals were included in the study placebo. O’Neil et al., used a smaller dose of semaglutide
(2,350 in the semaglutide group and 1,263 in the placebo that was given once daily at 0.05 mg to 0.4 mg. The course
group). Baseline characteristics were similar between both of treatment was 68 weeks for Wilding, Rubino and
groups in the 4 individual trials. The mean weight, BMI, Wadden et al., but only 52 weeks for O’Neil et al.’s study.
age and sex of the participants included in the trials are All trials reported percent change in body weight from
shown in Table 2. All were adults ≥18 years old with a baseline until the end of study as well as most common
BMI of ≥30 kg/m2 or ≥27 kg/m2 with at least 1 treated or adverse events associated with treatment (Table 1).
untreated weight-related comorbidity without diabetes.
The most common comorbidities were hypertension Risk of bias
and dyslipidemia. The study of Wilding et al., used once
weekly semaglutide injected subcutaneously starting at a Summary of the risk of bias is shown in Figure 2. The risk of
dose of 0.25 mg and escalated every 4 weeks until the target bias is generally low for all studies. However, we deemed
dose of 2.4 mg was reached. However, unlike the other 2 the risk of attrition bias questionable since in all 4 studies,

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68 Hanna Clementine Tan, et al Semaglutide for Weight Loss in Obesity Without Diabetes

Table 1. Characteristics of the studies included in the systematic review and meta-analysis
First author, Study Study
Inclusion criteria Exclusion criteria Interventions Outcome
year design population
O’Neil, 2018 RCT ≥ 18 yo with BMI ≥30 kg/m with no
2
Diabetes Semaglutide injected subQ once Percent change
BMI ≥30 kg/m2 weight fluctuation more than daily at one of the following doses in bodyweight
5 kg in the 90 days before (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg, from baseline
screening 0.4 mg) or liraglutide (3.0 mg). to week 52
Undergone at least one Doses started at 0.05 mg and most common
unsuccessful non- surgical incrementally escalated every reported
weight-loss attempt 4 weeks to the next level until adverse events
Free from major depressive reaching the final doses vs placebo
symptoms of equal injection volume.
Rubino, 2021 RCT ≥ 18 yo with At least 1 self-reported Diabetes, HbA1c 6.5% or Semaglutide started at 0.25 Percent
BMI ≥30 kg/m2 unsuccessful dietary effort togreater mg given subQ once weekly, change in body
or a BMI ≥27 lose weight More than 5 kg change in increased every 4 weeks until 2.4 weight from
kg/m with at
2
BMI of 27 kg/m2 or higher body weight within 90 days mg by week 16, and continued randomization
least 1 treated with at least 1 treated or of screening. to week 20, then randomized, to (week 20) to
or untreated untreated weight-related continue semaglutide or switch to week 68
weight-related comorbidity (hypertension, matching placebo for 48 weeks plus Most common
comorbidity dyslipidemia, obstructive lifestyle intervention with monthly reported
sleep apnea, cardiovascular counseling, reduced calorie diet, adverse events
disease) increased physical activity
Wadden, 2021 RCT ≥ 18 yo with 1 or more unsuccessful Diabetes, HbA1c 6.5% or Semaglutide started at 0.25 mg Percent change
BMI ≥30 kg/m2 dietary effort to lose weight greater given subQ once weekly, with dose in body weight
or a BMI ≥27 BMI of 27 kg/m2 with at least More than 5 kg change escalation every 4 weeks until by week 68
kg/m2 with at 1 weight-related comorbidity in body weight within 90 reaching target dose of 2.4 mg by Most common
least 1 treated (hypertension, dyslipidemia, days of screening prior or week 16, continued until week 68 reported
or untreated obstructive sleep apnea, planned obesity treatment plus diet modification vs placebo adverse events
weight-related cardiovascular disease) with surgery or a weight
comorbidity loss device
Wilding, 2021 RCT ≥ 18 yo with 1 or more unsuccessful Diabetes, HbA1c 6.5% Semaglutide started at 0.25 mg Percent change
BMI ≥30 kg/m2 dietary effort to lose weight or greater history of given subQ once weekly, with dose in body weight
or a BMI ≥27 BMI of 27 kg/m with at least chronic pancreatitis, acute escalation every 4 weeks until
2
from baseline to
kg/m with at
2
1 weight-related comorbidity pancreatitis within 180 reaching target dose of 2.4 mg by week 68
least 1 treated (hypertension, dyslipidemia, days before enrollment, week 16, continued until week 68 Most common
or untreated obstructive sleep apnea, previous surgical obesity plus counseling sessions every 4 reported
weight-related cardiovascular disease) treatment, and use of anti- weeks on adhering to a reduced adverse events
comorbidity obesity medication within calorie diet and increased physical
90 days before enrollment activity vs placebo
yo – year old, BMI – body mass index, subQ – subcutaneously

Table 2. Summary of the trial participants’ baseline characteristics

Mean weight Mean weight Mean BMI Mean BMI Mean Age Mean Age Female sex – no. Female sex –
First author,
semaglutide placebo group semaglutide placebo group semaglutide placebo group (%) semaglutide no. (%) placebo
year
group (kg) (kg) group (kg/m2) (kg/m2) group (years) (years) group group
O’Neil, 2018 113.2 114.2 39.9 40.1 48 46 66/102 (65%) 88/136 (65%)
Rubino, 2021 96.5 95.4 34.5 34.1 47 46 429/535 (80.2%) 205/268 (76.5%)
Wadden, 2021 106.9 103.7 38.1 37.8 46 46 315/407 (77.4%) 180/204 (88.2%)
Wilding, 2021 105.4 105.2 37.8 38.0 46 47 955/1306 (73.1%) 498/655 (76%)

data for those who were lost to follow-up were included, which decreased the heterogeneity to 0% after removing
which could affect the mean weight difference. As for other the study by Wadden et al. (Figure 3B). On review of the
bias, it was also deemed questionable since all trials had methodology, a possible cause of the heterogeneity is that
confounding factors such as diet and exercise adherence in Wadden et al.,’s study, all participants received a very
that may have significantly affected the magnitude of low calorie diet of 1000-1200 kilocalories per day (kcal/
weight loss. day) for the first 8 weeks followed by 1200-1800 kcal/day
for the remainder of the study. They were also prescribed
All trials were double blinded, randomized, using physical activity of 100 minutes per week that was slowly
interactive web-based response system with identically increased to reach 200 minutes per week. The other studies
looking placebo and semaglutide. Hence, they are at low also prescribed reduced calorie diet and increased physical
risk for selection, detection and performance biases. activity, but only a 500 kcal deficit per day and 150 minute
of physical activity per week. The very low-calorie intake
Outcome of the meta-analysis as well as increased minutes of physical activity in Wadden
et al.’s study may have resulted in more weight loss
There was an 11.85% mean difference for weight reduction especially in the placebo group, causing a smaller mean
between the treatment groups, favoring semaglutide (mean weight difference compared to the other studies.
difference -11.85, 95%CI [-12.81,-10.90], p<0.00001, I2 43%)
(Figure 3A). There is heterogeneity in between trials with an Another outcome of this review is the risk for gastrointes-
I2 43%, P=0.16%. A sensitivity analysis was then performed, tinal adverse events (typically nausea, vomiting, diarrhea,

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Semaglutide for Weight Loss in Obesity Without Diabetes Hanna Clementine Tan, et al 69

Figure 3. (A) Forest plot showing the effect of semaglutide on mean weight difference versus placebo. (B) Sensitivity
analysis showing the effect of semaglutide on mean weight difference versus placebo.

Figure 4. (A) Forest plot showing the risk of gastrointestinal adverse events with semaglutide treatment versus placebo. (B)
Sensitivity analysis showing the risk of gastrointestinal adverse events with semaglutide treatment versus placebo.

constipation). The review showed that the risk of developing Even though the risk for gastrointestinal adverse events
gastrointestinal adverse events was 1.59 times more was statistically significant, the studies of Rubino, Wadden
likely with semaglutide treatment (RR 1.59, 95%CI [1.34, and Wilding et al., reported that the duration of the
1.88], p< 0.00001, I2 81%) (Figure 4A). However, between- adverse events was short, transient and resolved without
trial heterogeneity was high I2 81%, which prompted a discontinuation of treatment.
sensitivity analysis that decreased the heterogeneity to 68%
(Figure 4B). The major source of heterogeneity was with The consolidation of the 4 trials also showed that patients
the dose of semaglutide. Rubino, Wadden, and Wilding et given semaglutide were twice as likely to discontinue
al., all achieved a dose of 2.4 mg once weekly compared to treatment due to adverse events (RR 2.19, 95%CI
O’Neil et al., where participants received only 0.4 mg once [1.36,3.55], p=0.001, I2 32%) (Figure 5A). Individually, the
weekly subcutaneous injections. risk for discontinuation due to adverse events is 6% for
semaglutide group and 2.9% for placebo group.

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70 Hanna Clementine Tan, et al Semaglutide for Weight Loss in Obesity Without Diabetes

Figure 5. (A) Forest plot showing the risk of adverse events leading to discontinuation of treatment with semaglutide versus
placebo. (B) Forest plot showing the risk of serious adverse events with semaglutide treatment versus placebo.

Serious adverse events were defined by the study of Rubino, to 2021. Combining the results of the trials showed that
Wadden and O’Neil et al., as life threatening, results in semaglutide is indeed associated with weight loss with a
death, requires hospitalization or prolongation of existing mean difference of 11.85% compared with placebo. The
hospitalization, results in persistent disability/incapacity, subjects of the trials all had at least one unsuccessful non-
congenital anomaly/birth defect, important medical event surgical attempt to lose weight, and based on this meta-
(may jeopardize subject or may require medical/surgical analysis, a 5 to 10% weight reduction could be achieved
intervention to prevent outcomes listed previously but with semaglutide. However, it is important to consider
may not be immediately life-threatening or result in that the Rubino study randomized participants to continue
death or hospitalization), as preventing daily activities by with semaglutide treatment or placebo after the target dose
Wilding et al. These were reported to be uncommon. The was reached. This could have affected the results because
risk for developing serious adverse events was 1.6 times participants could have lost weight with initial treatment
more likely for semaglutide than placebo (RR1.60, 95%CI with semaglutide.
[1.24, 2.07], p=0.0003, I2 0%) (Figure 5B). O’Neil, Wilding
and Rubino et al.’s studies each mentioned that death was Patient adherence is an important factor in the treatment of
reported during the trial period, but was not considered to obesity, and pharmacologic treatment has been associated
be related to semaglutide or placebo treatment. No death with significant adverse events which lead to their
was reported in Wadden et al.’s study. Serious events were discontinuation.7 This prompted us to evaluate whether
mostly of gastrointestinal disorders and hepatobiliary semaglutide was also associated with significant adverse
disorders such as acute pancreatitis and cholelithiasis. events. Consolidating the trials showed nausea, vomiting,
constipation and diarrhea to be the most common adverse
Discussion events. The trials have reported that these were of mild
to moderate severity and short duration that resolved
Investigation for the use of semaglutide for obesity has without treatment. Moreover, adverse events leading
been underway because trials in diabetic patients have to discontinuation and serious adverse events were
shown that it is associated with weight loss. It is currently uncommon. Dosing frequency is also a factor in adherence
approved for the treatment of diabetes but not for obesity.6 to treatment and once weekly dosing was associated with
Patients with obesity sustain a 46% higher inpatient cost better adherence.9 With its mild, transient adverse events
compared to normal weight individuals. They also have and once weekly dosing, we can expect good adherence
27% more physician visits, outpatient costs and 80% with semaglutide. We observed that aside from the
higher expenses on prescription medications.14 administration of semaglutide, reduced calorie diet and
increased physical activity were also part of the intervention.
Guidelines have recommended weight loss of 5 to 10% to Hence, semaglutide alone probably will not be able to
improve metabolic function and health outcomes.15,16 A achieve an 11.85% weight loss. Despite these confounding
5% weight loss improves multi-organ insulin sensitivity15 factors, we still believe that semaglutide is a major factor in
whereas, a 5 to 10% weight loss was associated with 0.6 to weight reduction because the subjects all attempted to lose
1% reduction in HbA1c.16 This review evaluated 4 double weight prior to starting treatment but were unsuccessful.
blind RCTs involving 3,613 participants between 2018

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Semaglutide for Weight Loss in Obesity Without Diabetes Hanna Clementine Tan, et al 71

Since obesity has been increasing in prevalence worldwide Funding Source

and can cause serious complications like cardiovascular None.
disease and diabetes,2,3 safe and acceptable treatments
References
for this condition are crucial to prevent further health 1. Frühbeck G, Busetto L, Dicker D, et al. The ABCD of obesity: An EASO
complications. However, since the trials were all done position statement on a diagnostic term with clinical and scientific
implications. Obes Facts. 2019;12(2):131–6. PMID: 30844811. PMCID:
within a specified follow-up period, it is difficult to predict
PMC6547280. https://doi.org/10.1159/000497124.
whether there will be weight gain following disconti- 2. World Health Organization. Obesity and overweight. Available
nuation of treatment, and whether continuous treatment from: https://www.who.int/news-room/fact-sheets/detail/obesity-
and-overweight. Accessed 15 May 2021.
will be necessary. 3. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH.
The incidence of co-morbidities related to obesity and overweight:
A systematic review and meta-analysis. BMC Public Health. 2009;9:
Strengths and limitations 88. PMID: 19320986. PMCID: PMC2667420. https://doi.org/10.1186/
1471-2458-9-88.
The study presented a comprehensive systematic review 4. van Bloemendaal L, ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant
M. Effects of glucagon-like peptide 1 on appetite and body weight:
and meta-analysis on semaglutide versus placebo for weight Focus on the CNS. J Endocrinol. 2014;221(1):T1-16. PMID: 24323912.
loss in patients who are obese without diabetes. It was https://doi.org/10.1530/JOE-13-0414.
5. Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical
able to show the percent mean weight loss after treatment treatment for obesity: A systematic review and meta-analysis of
with semaglutide as well as the risks for gastrointestinal randomised controlled trials. BMJ. 2013;347:f5934. PMID: 24149519.
adverse effects, discontinuation of treatment and serious PMCID: PMC3806364. https://doi.org/10.1136/bmj.f5934.
6. Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN.
adverse events. However, this review is limited to the 4 Semaglutide as a promising antiobesity drug. Obes Rev. 2019;20(6):
trials available for this meta-analysis and did not include 805–15. PMID: 30768766. https://doi.org/10.1111/obr.12839.
7. Ammori BJ, Skarulis MC, Soran H, Syed AA, Eledrisi M, Malik RA.
unpublished literature. Bias may have occurred from Medical and surgical management of obesity and diabetes: What’s
these limitations. Furthermore, the studies included the new? Diabet Med. 2020;37(2):203-10. PMID: 31850536. https://doi.
org/10.1111/dme.14215.
weight for participants who were lost to follow-up and this
8. Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide
could have affected the mean percent weight difference. versus once-daily liraglutide in metformin-treated patients with type
The adherence of the participants to treatment during the 2 diabetes (AWARD-6): A randomised, open-label, phase 3, non-
inferiority trial. Lancet. 2014;384(9951):1349–57. PMID: 25018121.
trial is also a factor. Each study has their own diet plan https://doi.org/10.1016/S0140-6736(14)60976-4.
and exercise program for the participants in addition to 9. Qiao Q, Ouwens MJNM, Grandy S, Johnsson K, Kostev K. Adherence
to GLP-1 receptor agonist therapy administered by once-daily or
treatment, which could also have affected the magnitude once-weekly injection in patients with type 2 diabetes in Germany.
of the effect estimate. Diabetes Metab Syndr Obes. 2016;9:201-5. PMID: 27418849. PMCID:
PMC4934555. https://doi.org/10.2147/DMSO.S99732.
10. Johnston SS, Nguyen H, Felber E, et al. Retrospective study of
Conclusion and recommendations adherence to glucagon-like peptide-1 receptor agonist therapy in
patients with type 2 diabetes mellitus in the United States. Adv
Ther. 2014;31(11):1119–33. PMID: 25408484. https://doi.org/10.1007/
In summary, among individuals with obesity without s12325-014-0166-0.
T2DM, subcutaneous semaglutide is effective for weight 11. Madsbad S. Review of head-to-head comparisons of glucagon-
loss with an 11.85% reduction from baseline compared to like peptide-1 receptor agonists. Diabetes Obes Metab. 2016;18(4):
317-32. PMID: 26511102. PMCID: PMC5064617. https://doi.org/10.1111/
placebo. This supports the use of semaglutide for weight dom.12596.
management in obesity. However, risk of gastrointestinal 12. Dhruv U, Gupta OP. Glucagon like peptide 1 receptor agonists:
Glycaemic control and beyond. J Clin Diabetol. 2016;2(4):18–25.
adverse events, discontinuation of treatment, and serious http://jcdonline.in/wp-content/uploads/2016/06/6.-JCD_Vol_2_
adverse events were higher in the semaglutide group No_4_Urman-Dhruv.pdf.
13. Capehorn MS, Catarig AM, Furberg JK, et al. Efficacy and safety of
versus placebo. RCTs with longer follow-up are needed
once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as
to determine long term efficacy, safety and risk for weight add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes
gain after treatment discontinuation. Subjects of the trials (SUSTAIN 10). Diabetes Metab. 2020;46(2):100–9. PMID: 31539622.
https://doi.org/10.1016/j.diabet.2019.101117.
were also mostly of the white race, hence, future research 14. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical
can focus on its efficacy and safety on the Asian population. spending attributable to obesity: Payer-and service-specific estimates.
2009;28(5):w822-31. PMID: 19635784. https://doi.org/10.1377/hlthaff.
28.5.w822.
Statement of Authorship 15. Magkos F, Fraterrigo G, Okunade AL, et al. Clinical and Translational
All authors certified fulfillment of ICMJE authorship criteria. Report Effects of moderate and subsequent progressive weight
loss on metabolic function and adipose tissue biology in humans
Author Contribution Statement with obesity. Cell Metab. 2016;23(24):591–601. PMID: 26916363.
PMCID: PMC4833627. https://doi.org/10.1016/j.cmet.2016.02.005.
HCT, OAD, MMM conceived the study; developed the
16. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS
methodology; synthesized the data and prepared the original Guideline for the management of overweight and obesity in adults:
draft. HCT and OAD validated the research; reviewed and edited A report of the American College of Cardiology/American Heart
the manuscript. HCT and MMM conducted the research. HCT Association Task Force on Practice Guidelines and The Obesity
Society. J Am Coll Cardiol. 2014;63(25 Pt 5):2985–3023. PMID: 24239920.
presented the data and coordinated the research activity planning.
https://doi.org/10.1016/j.jacc.2013.11.004.
OAD supervised the research. 17. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly
subcutaneous semaglutide vs placebo on weight loss maintenance in
Author Disclosure adults with overweight or obesity: The STEP 4 randomized clinical trial.
OAD reports receiving consulting fees from Eli Lilly and Novo JAMA. 2021;325(14):1414-25. PMID: 33755728. PMCID: PMC7988425.
https://doi.org/10.1001/jama.2021.3224.
Nordisk for service outside the submitted work, as well as 18. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide
honoraria for speaking engagements from Astra Zeneca, Novo in adults with overweight or obesity. N Engl J Med. 2021;384(11):
Nordisk, and Eli Lilly outside the submitted work. HCT and MMM 989-1002. PMID: 33567185. https://doi.org/10.1056/nejmoa2032183.
declare no conflict of interest in association with this study.

Vol. 37 No. 2 November 2022 www.asean-endocrinejournal.org

72 Hanna Clementine Tan, et al Semaglutide for Weight Loss in Obesity Without Diabetes

19. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous 20. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of
semaglutide vs placebo as an adjunct to intensive behavioral semaglutide compared with liraglutide and placebo for weight loss
therapy on body weight in adults with overweight or obesity: in patients with obesity: A randomised, double-blind, placebo and
The STEP 3 randomized clinical trial. JAMA - J Am Med Assoc. active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):
2021;325(14):1403-13. PMID: 33625476. PMCID: PMC7905697. https:// 637-49. https://doi.org/10.1016/S0140-6736(18)31773-2.
doi.org/10.1001/jama.2021.1831.

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