Laser Acupuncture versus Liraglutide in Treatment of Obesity: A Multi-Institutional Retrospective Cohort Study

Abstract

Background: Obesity is a global concern, driving the search for alternative treatments beyond lifestyle changes and medications. Laser acupuncture (LA) shows promise in obesity management, yet few studies compare it with FDA-approved medications. This study aimed to assess and compare LA’s impact with liraglutide on weight reduction in obese individuals. Methods: Data from the Chang Gung Research Database (CGRD) (2013–2018) were analyzed. Primary outcomes included changes in body weight and BMI within 180 days, with secondary outcomes measuring the proportion achieving 5%, 10%, and 15% weight loss. Adverse events were also assessed. Results: Of 745 subjects (173 LA users, 572 liraglutide users), LA users lost more weight by day 180 (5.82 ± 4.39 vs. 2.38 ± 5.75 kg; p < 0.001) and had a greater BMI reduction (−2.27 ± 1.73 vs. −0.93 ± 2.25 kg/m2; p < 0.001). More LA users achieved 5% and 10% weight loss compared to liraglutide users (64.2% vs. 22.7%, 26.6% vs. 4.2%; all p < 0.001). After balancing baseline differences, LA’s benefits remained significant. No adverse events were reported with LA. Conclusions: LA may offer superior weight reduction compared to liraglutide. Future studies should explore LA alone or in combination with liraglutide for obesity management.

Full text

Healthcare 2024, 12, 1279. https://doi.org/10.3390/healthcare12131279 www.mdpi.com/journal/healthcare
Article
Laser Acupuncture versus Liraglutide in Treatment of Obesity:
A Multi-Institutional Retrospective Cohort Study
Wen -Lin Yu 1,†, Yu-Ning Liao 1,†, Tsung-Hsien Yang 1, Ching-Wei Yang 1,2, Ting-I Kao 1, Pai-Wei Lee 3, Chiu-Yi Hsu 3,
Jhen-Ling Huang 3, Yu-Tung Huang 3 and Hsing-Yu Chen 1,2,4,*
1 Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine,
Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; mr3099@cgmh.org.tw (W.-L.Y.);
x1991425@cgmh.org.tw (Y.-N.L.); 8905001@cgmh.org.tw (T.-H.Y.); ycw0426@gmail.com (C.-W.Y.)
2 School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
3 Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou Medical Center,
Tao yua n 333, Taiwan; wei.lee@parexel.com (P.-W.L.); joy960111@gmail.com (C.-Y.H.);
cratwoy0309@gmail.com (J.-L.H.)
4 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University,
Tao yua n 333, Taiwan
* Correspondence: 8705016@cgmh.org.tw
† These authors contributed equally to this work.
Abstract: Background: Obesity is a global concern, driving the search for alternative treatments
beyond lifestyle changes and medications. Laser acupuncture (LA) shows promise in obesity
management, yet few studies compare it with FDA-approved medications. This study aimed to
assess and compare LA’s impact with liraglutide on weight reduction in obese individuals.
Methods: Data from the Chang Gung Research Database (CGRD) (2013–2018) were analyzed.
Primary outcomes included changes in body weight and BMI within 180 days, with secondary
outcomes measuring the proportion achieving 5%, 10%, and 15% weight loss. Adverse events were
also assessed. Results: Of 745 subjects (173 LA users, 572 liraglutide users), LA users lost more
weight by day 180 (5.82 ± 4.39 vs. 2.38 ± 5.75 kg; p < 0.001) and had a greater BMI reduction (−2.27 ±
1.73 vs. −0.93 ± 2.25 kg/m2; p < 0.001). More LA users achieved 5% and 10% weight loss compared to
liraglutide users (64.2% vs. 22.7%, 26.6% vs. 4.2%; all p < 0.001). After balancing baseline differences,
LA’s benefits remained significant. No adverse events were reported with LA. Conclusions: LA
may offer superior weight reduction compared to liraglutide. Future studies should explore LA
alone or in combination with liraglutide for obesity management.
Keywords: laser acupuncture; integrative and complementary medicine; obesity; body weight loss
1. Introduction
In modern society, obesity has become a worldwide problem due to high-calorie
diets and sedentary lifestyles. The prevalence of obesity has been increasing in the past
decades [1–4]. According to the definition established by the World Health Organization,
individuals in the Asia–Pacific region with a body mass index (BMI) > 23 kg/m2 and >25
kg/m2 are deemed overweight and obese, respectively. Obesity has been linked to an
increased risk of various diseases, including cardiovascular diseases [5,6], osteoarthritis,
type 2 diabetes, dyslipidemia, polycystic ovary syndrome [7], non-alcoholic fay liver
disease, malignancies, obstructive sleep apnea, and depression [8–10]. Additionally,
evidence has suggested that individuals who are overweight or obese are at a higher risk
of mortality, and that these conditions are associated with a substantially increased
burden on healthcare. Therefore, studies focusing on the management of obesity are
warranted [1].
Citation:
Yu, W.-L.; Liao, Y.-N.;
Yan g, T.
-H.; Yang, C.-W.; Kao, T.-I.;
Lee, P.
-W.; Hsu, C.-Y.; Huang, J.-L.;
Huang, Y.
-T.; Chen, H.-Y. Las er
Acupuncture versus Liraglutide in
Treatment of Obesity: A Multi
-
Institutional Retrospective Cohort
Study.
Healthcare 2024, 12, 1279.
hps://doi.org/10.3390/
healthcare12131279
Academic Editor:
Luís Carlos Matos
Received:
6 April 2024
Revised:
15 June 2024
Accepted:
16 June 2024
Published:
26 June 2024
Copyright:
© 2024 by the authors.
Licensee MDPI, Basel,
Swierland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Aribution (CC BY) license
(hps://creativecommons.org/license
s/by/4.0/).

Healthcare 2024, 12, 1279 2 of 14
Currently, available therapeutic strategies for weight loss include dieting, lifestyle
modifications, exercise, and the use of anti-obesity agents. Research indicates that
exercise, diet control, medication, and surgery could result in small-to-modest reductions
in body weight [11,12]. Lifestyle modification, including calorie limiting and regular
physical activity, is the first-line treatment for alleviating obesity. However, maintaining
these efforts over a long period can be challenging because of the busy modern lifestyle
and poor execution ability [13,14]. Research indicates that consuming anthocyanins
significantly reduces body weight, fat mass, and inflammation in murine obesity models,
but human studies are lacking [15]. Surgery can be the most effective option for reducing
body weight; however, the potential side effects of surgery (e.g., vitamin deficiency,
gastroesophageal reflux, and dumping syndrome) remain a concern [12,16]. Therefore,
medications for the management of obesity have become a mainstream approach to body
weight reduction. The Food and Drug Administration (FDA) has approved orlistat,
phentermine, phentermine/topiramate extended-release, naltrexone/bupropion, and two
glucagon-like peptide-1 (GLP-1) agonists (liraglutide and semaglutide) for weight control
[16]. Liraglutide promotes weight loss by inducing the feeling of fullness and delaying
gastric emptying, leading to decreased food intake [17]. According to the SCALE trial,
among patients with diabetes mellitus (DM), 15.9% of liraglutide users lost 10% of their
body weight [18]. Moreover, liraglutide reduced body weight in obese individuals
without DM [19]. Nevertheless, the occurrence of adverse events (e.g., nausea and
elevated risk of cholelithiasis, cholecystitis, and pancreatitis) may limit the use of
liraglutide [20].
In addition to Western medicine, the use of complementary and alternative medicine
(CAM) for obesity management currently has numerous adherents. This is primarily
aributed to intolerance to Western medicine or concerns regarding side effects [21].
Several studies reported that laser acupuncture (LA) and diet control reduced the waist-
to-hip ratio, BMI, and appetite in obese individuals compared with sham treatment [22–
24]. A systematic review also indicated that LA might positively affect obesity by reducing
body weight, body fat, and appetite [25]. However, due to the small sample sizes and
relatively short treatment duration, it is difficult to draw a robust conclusion regarding
using LA to alleviate obesity. Additionally, most studies compared the effects of LA to
those of placebo or sham treatment. Hence, it remains unclear whether the effectiveness
of LA in reducing body weight is comparable to that of FDA-approved medications.
This real-world cohort study aimed to compare the effects of LA and liraglutide on
body weight reduction among obese individuals. By obtaining results from real-world
data, we can evaluate the effectiveness of LA in daily clinical practice before conducting
clinical trials in the future.
2. Materials and Methods
2.1. Data Source
We collected data from the Chang Gung Research Database (CGRD), which records
procedures, medications, laboratory data, and examinations from outpatient, inpatient,
and emergency visits at the Chang Gung Memorial Hospital (CGMH). CGMH is the
largest hospital system in Taiwan, with eight medical institutes, including 10,070 beds
with >280,000 inpatient admissions, >8,500,000 visits to the outpatient department, and
500,000 visits to the emergency department annually [26]. The CGRD covers a significant
portion of the Taiwanese population, accounting for 12.2% and 21.2% of inpatient and
outpatient services, respectively, between 1997 and 2020 [27]. The enormous amount of
available medical data renders the CGRD an excellent resource for clinical studies
[11,26,28].

Healthcare 2024, 12, 1279 3 of 14
2.2. Study Design and Subjects
We collected all feasible patient data from 1 January 2013 to 31 December 2018.
Patients diagnosed with obesity or metabolic syndrome, confirmed by the International
Classification of Diseases, Tenth Revision and Ninth Revision, Clinical Modification (ICD-
10-CM and ICD-9-CM) codes, were selected. These codes included ICD-9-CM codes
278.00, 278.01, 278.03, 649.10-14, 793.91, V85.30-39, V85.41-45, and V85.54, and ICD-10-CM
codes E65, E668, and E669. The first day of LA or liraglutide use was set as the index date.
The baseline body weight was determined as the highest body weight recorded one month
before and after the index date, and the BMI was calculated using the height of each
subject.
The inclusion criteria were (1) age ≥ 18 and ≤75 years; (2) BMI ≥ 27 kg/m2 and at least
one weight-related comorbidity, such as DM, dyslipidemia, hypertension, or a fay liver
360 days before the index date; and (3) at least two treatments with LA or liraglutide after
the index date. Subjects with missing data on weight or height at baseline or day 180, as
well as those who used other anti-obesity medications or who had a history of bariatric
surgery, were excluded (Figure 1).
Figure 1. Flow diagram of this study. Abbreviations: CGRD, Chang Gung Research Database; LA,
laser acupuncture.
2.3. Intervention and Comparisons
The liraglutide group received subcutaneous liraglutide according to the
recommended dosing scheme for obesity. The LA group received LA three to four times
per week on fixed acupoints from a qualified practitioner of traditional Chinese medicine.
The choice of acupoints and frequency of LA was based on the study conducted in 2010
by Dr. Wen-Long Hu [24]. The selected acupoints were as follows (Figure 2,
Supplementary Table S1): stomach and hunger (auricular points; B6 for right ear and B7
for left ear), ST25 (Tianshu, B2), ST28 (Shuidao, B2), ST40 (Fenglong, B2), SP15 (Daheng,
B2), and CV9 (Shuifen, B3) [24]. Energy (0.5 J) was applied to each of the above points via
a gallium aluminum arsenide Handylaser Trion (RJ-Laser; Reimers & Janssen GmbH,
Waldkirch, Germany) with the following seings: maximal power, 50 mW; wavelength,
785 nm; area of probe, 0.03 cm2; power density, 50 mW/cm2.

Healthcare 2024, 12, 1279 4 of 14
Figure 2. Schematic diagram of acupoints used for laser acupuncture (LA). The unit for precise
acupoint localization is the Proportional Bone Cun (B-cun). The following measurements were
defined: 8 B-cun for the distance between the two nipples; 5 B-cun for the length from the umbilicus
to the superior border of the pubic symphysis; 8 B-cun for the length from the midpoint of the
xiphisternal synchondrosis; and 16 B-cun for the length from the prominence of the lateral malleolus
to the popliteal crease to the umbilicus (edited with BioRender).
2.4. Covariates
Covariates including age, gender, height, body weight, mean arterial pressure, and
underlying comorbidities (e.g., hypertension, dyslipidemia, ischemic heart disease,
cerebrovascular diseases, chronic pulmonary disease, DM, chronic hepatitis, non-
alcoholic steatohepatitis) were collected. The Charlson comorbidity index (CCI) was also
calculated to summarize the comorbidities (the diagnostic codes are listed in
Supplementary Tab le S2). The use of diagnostic codes at least twice in outpatient visits or
once during admissions six months before the index date denoted the occurrence of the
abovementioned comorbidities. The worst value recorded within six months before the
index date was used to retrieve biochemical profiles, including aspartate transaminase,
alanine transaminase, blood urea nitrogen, creatinine, hemoglobin A1c, fasting sugar,
total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein.
2.5. Outcome Assessment
The primary outcome of this study was the change in body weight from baseline to
day 180. The secondary outcome was the proportion of subjects who lost at least 5%, 10%,
and 15% of their baseline weight. We also assessed the temporal changes in body weight
at days 30, 60, 90, 120, and 150. Any newly diagnosed ICD codes used during admissions
or emergency visits within the 180-day treatment course were regarded as adverse events,
including hypertension, ischemic stroke, hemorrhagic stroke, and cardiovascular
disorders (the diagnostic codes are listed in Supplementary Table S 2).
2.6. Statistical Analysis
The baseline covariates were described, and inference statistics were performed to
examine the differences between the LA and liraglutide. Furthermore, overlap weighting
was used to overcome the potential confounding bias caused by differences in
demographic features and imbalance in LA and liraglutide users. Overlap weighting is a
statistical method commonly used in observational studies that rely on propensity scores
(PS) to mimic the randomization process of clinical trials, especially when there are
imbalances between groups [29]. First, baseline covariates, including age, gender, body
weight, and CCI, were used to generate the PS for using LA. Second, the values of 1-PS

Healthcare 2024, 12, 1279 5 of 14
and PS were assigned to the LA group and liraglutide group, respectively, as weights
when estimating the outcomes. The absolute standardized mean difference (ASMD) was
used to demonstrate the differences between LA and liraglutide groups with overlap
weighting. Sensitivity tests were conducted with other PS-related models, such as 1:1
propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)
with the same PS value as overlap weighting to verify the consistency of the results. The
differences in weight change between LA and liraglutide users at each time point were
examined using independent t-tests. Pearson X2 statistics were used to compare the
proportions of subjects who achieved 5%, 10%, and 15% weight reduction, as well as the
rates of adverse events between the two groups. Repeated ANOVA was used to examine
the treatment effects within and between the LA and liraglutide users. The effect size was
calculated with a 95% confidence interval (CI) for proportional data. Statistical
calculations were performed using the commercially available software SAS Studio 3.4
(SAS, Cary, NC, USA), with p-values < 0.05 denoting statistically significant differences,
and Bonferroni correction was used when multiple comparisons were performed.
3. Results
3.1. Baseline Characteristics of Subjects
A total of 745 eligible subjects were included in the analysis, of which 173 (23.2%)
were LA users. The baseline characteristics of these two groups are summarized in Table
1. Compared with liraglutide users, LA users were younger (51.7 ± 11.7 vs. 41.7 ± 11.0
years, respectively) and predominantly female (50.7% vs. 83.8%, respectively; p < 0.001).
In addition, LA users had lower baseline body weight than liraglutide users (81.4 ± 13.1
vs. 87.1 ± 16.9 kg, respectively; p < 0.001). Moreover, compared with liraglutide users, LA
users had a lower prevalence of comorbidities, including hypertension (61.9% vs. 11%),
dyslipidemia (66.4% vs. 12.1%), DM (78.7% vs. 6.4%), ischemic heart disease (12.1% vs.
1.2%), chronic hepatitis (11.9% vs. 2.9%), and lower CCI (2.31 ± 1.61 vs. 0.35 ± 0.78) (all p <
0.001). Regarding the biochemical and physiological profiles, liraglutide users almost had
significantly higher values for BMI, aspartate transaminase, alanine transaminase, blood
urea nitrogen, creatinine, hemoglobin A1c, and fasting sugar than LA users. However,
lower mean arterial pressure was noted in the LA group compared with the liraglutide
group (129.2 ± 15.6 vs. 132.5 ± 15.6 mmHg; p = 0.018). Concerning the lipid profile,
compared with the liraglutide group, the LA group had significantly higher high-density
lipoprotein (39.8 ± 9.8 vs. 44.3 ± 8.5 mg/dL; p = 0.013) and low-density lipoprotein (104.8 ±
32.7 vs. 125.2 ± 24.3 mg/dL; p < 0.001) but lower triglyceride levels (233.3 ± 229.9 vs. 151.8
± 75.8 mg/dL; p < 0.001). We used overlap weighting to eliminate the differences in baseline
features between the two groups in terms of age, gender, CCI, and body weight (Table 1).
Table 1. Baseline demographic characteristics of LA and liraglutide users.
LA Users
Liraglutide Users
p-Value
Overlap Weighting
ASMD
(n = 173)
(n = 572)
LA Users
Liraglutide Users
Demographics
Age, years
41.7 ± 11.0
51.7 ± 11.7
<0.001
45.4 ± 6.4
45.4 ± 3.9
0.000
Gender (n, %)
<0.001
0.000
Male
28 (16.2%)
282 (49.3%)
26.2%
26.2%
Female
145 (83.8%)
290 (50.7%)
73.8%
73.8%
Comorbidities
Hypertension
19 (11%)
354 (61.9%)
<0.001
21.5%
36.8%
0.343
Dyslipidemia
21 (12.1%)
380 (66.4%)
<0.001
20.4%
50.2%
0.656
Ischemic heart diseases
2 (1.2%)
69 (12.1%)
<0.001
1.7%
6.0%
0.225
CVD
2 (1.2%)
15 (2.6%)
0.386
2.53%
0.05%
0.221
CPD
8 (4.6%)
34 (5.9%)
0.513
10.44%
0.59%
0.442

Healthcare 2024, 12, 1279 6 of 14
DM
11 (6.4%)
450 (78.7%)
<0.001
14.7%
67.1%
1.260
Chronic hepatitis
5 (2.9%)
68 (11.9%)
<0.001
7.0%
2.0%
0.242
NAFLD
1 (0.6%)
10 (1.8%)
0.472
0.70%
1.16%
0.048
CCI
0.35 ± 0.78
2.31 ± 1.61
<0.001
0.81 ± 0.66
0.81 ± 0.21
0.000
Biochemical and physiological profiles
MAP, mmHg
132.5 ± 15.6
129.2 ± 15.6
0.018
135.2 ± 9.5
132.1 ± 5.5
0.399
Body weight, kg
81.4 ± 13.1
87.1 ± 16.9
<0.001
83.9 ± 9.0
83.9 ± 5.2
0.000
BMI, kg/m
2
31.6 ± 4.8
33.8 ± 6.9
<0.001
32.0 ± 2.7
33.3 ± 2.6
0.501
AST, mg/dL
31.1 ± 15.3
50.3 ± 83.9
0.005
33.9 ± 12.9
44.4 ± 15.5
0.736
ALT, mg/dL
36.3 ± 27.3
49.8 ± 48.7
0.001
41.9 ± 21.4
49.5 ± 13.7
0.421
BUN, mg/dL
12.3 ± 3.1
26.4 ± 19.7
<0.001
12.5 ± 2.3
16.5 ± 2.4
1.667
Creatinine, mg/dL
0.66 ± 0.14
1.13 ± 1.04
<0.001
0.69 ± 0.11
0.81 ± 0.12
1.053
HbA1C, %
6.4 ± 0.8
9.7 ± 1.7
<0.001
6.6 ± 0.7
9.5 ± 0.6
4.802
Fasting glucose, mg/dL
104.2 ± 24.0
214.5 ± 72.6
<0.001
113 ± 18.4
201.2 ± 22.6
4.284
Lipid profile
Total cholesterol, mg/dL
197.9 ± 30.1
185.8 ± 44.7
0.051
199.9 ± 22.8
191.5 ± 13.4
0.449
Triglyceride, mg/dL
151.8 ± 75.8
233.3 ± 229.9
<0.001
161.4 ± 61.8
224.3 ± 51.8
1.103
LDL cholesterol, mg/dL
125.2 ± 24.3
104.8 ± 32.7
<0.001
125.6 ± 18.7
112.2 ± 11.3
0.869
HDL cholesterol, mg/dL
44.3 ± 8.5
39.8 ± 9.8
0.013
43.8 ± 6.9
40.88 ± 3.2
0.543
Continuous covariates are presented as the mean ± standard deviation, while categorical covariates
are presented as a number (percentage). The covariates were balanced using the absolute
standardized mean difference (ASMD). An ASMD ≤ 0.1 indicates a negligible difference in potential
confounders between the two study groups. Abbreviations: ALT, alanine transaminase; AST,
aspartate transaminase; BUN, blood urea nitrogen; CCI, Charlson comorbidity index; CPD, chronic
pulmonary disease; CVD, cerebrovascular diseases; DM, diabetes mellitus; HDL, high-density
lipoprotein; NAFLD, non-alcoholic fay liver disease; LA, laser acupuncture; LDL, low-density
lipoprotein; MAP, mean arterial pressure.
3.2. Assessment of Body Weight Changes
LA users exhibited a two-fold more significant weight loss than liraglutide users after
180 days of intervention (5.82 ± 4.39 vs. 2.37 ± 5.75 kg; p < 0.001) (Figure 3A). Throughout
the study, there was a notable difference in the paern of body weight reduction between
and within the two groups. Liraglutide users significantly reduced body weight during
the first month, whereas LA users experienced a significant reduction during the first 90
days (Figure 3A). The trend of body weight reduction was similar with overlap weighting
liraglutide and LA users (Figure 3B). Moreover, LA users had a two-fold greater reduction
in BMI than liraglutide users (−2.27 ± 1.73 vs. −0.93 ± 2.25 kg/m2 and −2.20 ± 1.07 vs. −0.81
± 0.66 kg/m2, with and without overlap weighting, respectively; all p < 0.001) (Table 2).
(A)
(B)
Figure 3. Changes in body weight during the 180 days of treatment (A) without overlap weighting
(p-values < 0.001 for both time and treatment effects; F values for time factor: 19468; and F values for
treatment factor: 153633) and (B) with overlap weighting (p-values < 0.001 for the overall and both

Healthcare 2024, 12, 1279 7 of 14
the time and treatment effects; F values for time factor: 10460; and F values for treatment factor:
67923). Abbreviations: LA, laser acupuncture.
Table 2. Changes in primary endpoints from baseline to day 180, with and without overlap
weighting.
Without Overlap Weighting
With Overlap Weighting
LA Users
(n = 173)
Liraglutide
Users
(n = 572)
t or z, p-
Value
(between
Group)
LA Users Liraglutide
Users
t or z, p-
Value
(between
Group)
Changes in body weight
Weight, kg
−5.82 ± 4.39
(−6.48, −5.16)
−2.37 ± 5.75
(−2.84, −1.90)
−7.28, <0.001
−5.77 ± 2.82
(−6.19, −5.35)
−1.95 ± 1.39
(−2.06, −1.84)
−24.14, <0.001
Within group t, p-value
7.82, <0.001
3.18, 0.002
8.07, <0.001
8.74, <0.001
% of body weight −7.16 ± 0.05
(−7.17, −7.15)
−2.62 ± 0.05
(−2.63, −2.62)
−1045.16,
<0.001
−6.83 ± 0.03
(−6.84, −6.83)
−2.33 ± 0.02
(−2.33, −2.33)
−1851.85,
<0.001
Loss >5% (%)
64.2
22.7
10.225 <0.001
61.1
19.7
10.482, <0.001
Loss >10% (%)
26.6
4.2
8.8456, <0.001
27.5
5.1
8.493, <0.001
Loss >15% (%)
6.9
1.2
4.1885, <0.001
6.1
1.6
3.232, 0.002
Changes in BMI
−2.27 ± 1.73 −0.93 ± 2.25 −8.29, <0.001 −2.20 ± 1.07 −0.81 ± 0.66 −16.20, <0.001
Within group t, p-value
5.86, <0.001
3.05, 0.002
10.00, <0.001
7.34, <0.001
Continuous covariates are presented as the mean ± standard deviation, while categorical covariates
are presented as a number (percentage). The p-values were calculated by Student t-test and
Pearson’s chi-squared test for continuous and categorical covariates, respectively. Paired t-tests were
used to compare the within-group weight and BMI changes. Abbreviations: BMI, body mass index;
LA, laser acupuncture
A significantly higher proportion of LA users achieved the goal of >5% weight loss
compared with liraglutide users (64.2% vs. 22.7%; effect size: 6.09, 95% CI: 4.22–8.79; p <
0.001). Similar trends were observed for >10% (26.6% vs. 4.2%; effect size: 8.27, 95% CI:
4.87–14.05; p < 0.001) and >15% (6.9% vs. 1.2%; effect size: 6.02, 95% CI: 2.33–15.53; p <
0.001) weight loss. With overlap weighting, a similar trend in body weight loss was
observed in both LA and liraglutide users. Most LA and liraglutide users lost 5–10% and
>5% of their body weight, respectively (Figures 4 and 5). Additionally, sensitivity analyses
with 1:1 PSM and IPTW were conducted. In 1:1 PSM, LA users lost more body weight
than liraglutide users (−5.67 ± 5.16 kg vs. −1.3 ± 3.27 kg, p < 0.001). This trend was consistent
in the IPTW model, with LA users showing greater weight loss than liraglutide users
(−5.92 ± 4.4 kg vs. −2.34 ± 2.97 kg, p < 0.001; Supplementary Tables S3 and S4). Interestingly,
increases in body weight were noted in both groups during the study period; however,
the proportion of subjects who experienced weight gain was markedly lower in the LA
group than in the liraglutide group (Figure 5).

Healthcare 2024, 12, 1279 8 of 14
Figure 4. Subjects achieving >5%, >10%, and >15% body weight loss after 180 days of treatment.
Abbreviations: LA, laser acupuncture.
Figure 5. Accumulated distribution of 5%, 10%, and 15% of body weight loss among LA and
liraglutide users. Abbreviations: LA, laser acupuncture.
3.3. Adverse Events
At the end of the trial, 17 liraglutide users had hypertension, and four had ischemic
heart disease, while there was no new-onset hypertension or ischemic heart disease
observed among LA users (Table 3). With balancing through 1:1 PS M, no significant
adverse events were observed during treatment in either group. In the IPTW model, there
was no adverse event in the LA users, but a lower risk of hypertension was noted
compared to liraglutide users (0% vs. 2.86%, p-value = 0.025; Supplementary Tab l e s S3 and
S4).
Table 3. Incidence of identifiable adverse events during the 180 days of treatments.
LA Users
Liraglutide Users
p-Value
(n = 173)
(n = 572)
Hypertension
0
17
0.017 *
Ischemic heart diseases
0
4
0.578 *
Hemorrhagic stroke
0
0
-
Ischemic stroke
0
0
-
* Fisher’s exact test. Abbreviations: LA, laser acupuncture.

Healthcare 2024, 12, 1279 9 of 14
4. Discussion
Our study results suggest that LA may be a more effective treatment option than
liraglutide use for reducing body weight. After 180 days of treatment, the LA group
experienced a mean reduction in body weight of 7.16% (5.82 ± 4.39 kg), which was
significantly greater than that recorded for the liraglutide group (2.62%; 2.37 ± 5.75 kg).
Given the nature of this cohort study, differences in the covariates between the LA and
liraglutide groups were expected, with certain factors such as gender, age, baseline
weight, and comorbidities potentially influencing the conclusions (Table 2). To address
this, we included these covariates in the PS models to balance the differences between
potential confounding variables. The reductions in body weight and BMI varied across
the PS models, indicating that, while these covariates may have been influential, their
impact on the overall conclusions was minimal. Different PS models utilizing the same
covariates yielded consistent results across various weighting and matching conditions.
This consistency indicated that the differences observed between or within the groups
receiving LA and liraglutides were reliable. Additionally, no adverse events were reported
in the LA group, indicating that LA may be a safer option for weight loss than liraglutide.
Based on a 2009 randomized controlled trial (RCT) published in The Lancet [30], and
another RCT published in The Lancet in 2017 [31], it has been demonstrated that once-daily
subcutaneous liraglutide, when combined with diet and exercise, can reduce body weight
by 4.8–6.5 kg. However, subjects with higher initial weights tend to experience a decrease
in the efficacy of liraglutide [32], which might explain why the mean weight reduction
observed with liraglutide in this observational study was similar to that seen in clinical
trials.
On the other hand, previous studies involving postmenopausal individuals have
shown that the combination of LA and a low-calorie diet can lead to a reduction of 9% in
body weight after 6 months of treatment [23]. A randomized control trial demonstrated
that LA significantly reduced postpartum weight by approximately 19% of the BMI after
36 weeks of treatment; of note, subjects in the sham group experienced only a 3%
reduction in BMI [33]. However, based on different study designs, weight and BMI
reduction varied significantly across different studies, with weight loss ranging from 3.17
to 16.33 kg and BMI reduction ranging from 1.45 to 6.72 kg/m2 [22–24,33–35]. These
discrepancies may be aributed to differences in study populations and the specific LA
seings used. Although these studies assessed the effect of LA in conjunction with dietary
restrictions and/or exercise, the weight reduction observed in our study (5.82 kg) was less
pronounced. This may be due to the observational nature of our study, where only diet
education could be provided during routine clinical practice. Rigorous dietary
restrictions, exercise protocols, and adherence could not be closely monitored, potentially
leading to less substantial weight reduction. Nonetheless, alongside previous studies, our
findings suggest the feasibility of using LA for body weight management, highlighting
the need for clinical trials to evaluate the effectiveness of our LA seings.
From the perspective of traditional Chinese medicine, obesity is often aributed to
an accumulation of phlegm-dampness. This condition is believed to result from irregular
dietary habits or impaired spleen function, leading to the accumulation of dampness,
which transforms into phlegm and causes obesity, like lipid deposition in liver or
subcutaneous tissues. Therefore, in acupuncture point selection, points along the spleen
and stomach meridians, such as ST25, ST28, ST40, and SP15, are chosen to enhance spleen
function and promote the elimination of dampness. Additionally, auricular points like
stomach and hunger are used to help control appetite and regulate water metabolism.
LA has demonstrated a favorable safety profile and higher effectiveness for weight
loss compared with other non-pharmacological interventions. Higher baseline body
weight may be associated with greater body weight loss; hence, the lower baseline body
weight and greater weight reduction observed in the LA group are intriguing [36].
Additionally, we observed no occurrence of significant systemic adverse events during
the study’s observation period. Considering LA’s non-invasive nature, it may become an

Healthcare 2024, 12, 1279 10 of 14
integrative and complementary treatment for obesity. It has been suggested that non-
invasive brain stimulation could assist in the management of obesity, yielding a significant
decrease in BMI (4–8%) and few adverse events (e.g., headache) [37,38]. Traditional needle
acupuncture could result in moderate reductions in body weight in overweight patients
(25 ≤ BMI < 30), with possible side effects including dizziness, nausea, fatigue and local
itching, tingling, minor inflammation, or pain at the acupuncture site [39,40]. Tsz Fung
Lam et al. reported that electro-acupuncture in treating central obesity could reduce BMI
−0.6 (95% CI = −0.9 to −0.3) in 8 weeks with adverse effects such as headaches, dizziness,
and insomnia [41]. Invasive body contouring can effectively remove localized areas of
adiposity from under the skin. However, the possibility of adverse events (e.g., prolonged
swelling, bruising, numbness, thrombophlebitis, and pulmonary embolism) raises
concerns [42]. Non-invasive body contouring techniques using high-intensity focused
ultrasound have shown promising results in reducing the circumference of the treated
area and skin fat thickness. However, of note, this procedure may not be suitable for
pregnant women, individuals with a BMI >30, or those with poor medical status [43]. In
summary, based on our findings, it can be inferred that LA may exert a significant weight
loss effect with good tolerability and minimal harm to individuals.
LA could be used as a non-pharmacologic adjunct therapy to enhance weight loss for
individuals receiving pharmacologic therapies, regardless of the potential drug
interactions. As a GLP-1 receptor agonist, liraglutide acts on GLP-1 receptors and
suppresses appetite in humans [44]. Liraglutide may reduce hunger signals and induce
the feeling of fullness by stimulating proopiomelanocortin (POMC) neurons and
inhibiting neuropeptide Y (NPY) and agouti-related peptide (AGRP) neurons in the
arcuate nucleus [45]. Thus, obese subjects who received GLP-1 experienced a reduction in
body weight due to a slower rate of gastric emptying and an extended period of
postprandial satiety [46]. The mechanisms underlying the effects of LA on weight
reduction and loss of appetite remain unclear [25]. For example, the acupoints on ears may
affect motility and the gastrointestinal tone by regulating the vagal nerve [47].
Additionally, from the perspective of traditional Chinese medicine, obese individuals
tend to have a phlegm-dampness constitution, which was reported as the main risk factor
of metabolic disorder [48]. The acupoints used in the present study aimed to reduce the
phlegm-dampness accumulation in the body by regulating qi deficiency and addressing
the resulting metabolism disorder [24]. Studies on animals and humans have indicated
that acupuncture reduces weight by regulating obesity-related neuropeptides (e.g.,
ghrelin, leptin, or serotonin) and reducing lipid levels [49,50]. Using functional magnetic
resonance imaging, Von Deneen et al. found that acupuncture can also stimulate several
neurophysiological pathways, and affected satiety hormones and the basal metabolic rate
[51]. Moreover, it has been reported that LA can improve glycemic control and markers
of insulin resistance. These effects could be complementary to the effects of GLP-1 agonists
on obesity [52].
Our results also revealed that 64.2% of LA users achieved a weight loss of 5–10% of
their baseline body weight compared with only 22.7% of liraglutide users. Previous
studies have shown that a 5–10% weight loss is associated with significant health benefits.
These benefits include a reduction in healthcare costs, improvement in glycemic outcomes
and quality of life, and reduction in the risk of metabolic diseases, cardiovascular disease,
hepatic steatosis, and structural damage to the knee joint [53,54]. It has been reported that
a body weight reduction of 10% in patients with type 2 diabetes may lower the risk of
acute myocardial infarction, stroke, or admission to hospital for angina by 21% [55].
Studies have demonstrated that weight loss promotes clinical improvement in patients
with non-alcoholic fay liver disease [56,57]. In the present study, the target of 5–10%
body weight reduction was achieved. Therefore, LA may help individuals achieve their
weight-loss goal and reduce the risk of comorbid diseases.

Healthcare 2024, 12, 1279 11 of 14
Limitations
The present study was subject to some limitations. Firstly, given that this
retrospective cohort study was based on patient data retrieved from the hospital database
and involved subjects seeking interventions other than diet education or exercise,
identifying patients treated with a placebo or those who did not receive any treatment to
serve as a control group was challenging. Consequently, we selected liraglutide users as
the active control group to emulate real-world situations since liraglutide is one of the
most potent FDA-approved medications for weight management. Secondly, we focused
on the treatment, diagnosis, and related biochemical and physical parameters of obesity.
Therefore, we may have overlooked information related to lifestyle modifications and
subject compliance to treatment with LA or liraglutide. However, the real-world nature
of this study may provide more realistic insight into the management of obesity. Thirdly,
as most subjects were collected at the CGMH, the cohort study was predominantly
composed of Asian individuals. It remains unclear whether these results are generalizable
to other ethnic groups. Fourthly, the long-term treatment effects of LA remain unknown,
as our study tracked the subjects for only 180 days. Fifthly, although the authors have
consensus based on the protocol provided by Dr. Wen-Long Hu [24,33], it is true that the
doctors may add other acupoints to relieve other symptoms or modify individuals’
constitution when managing body weight. However, it is acknowledged that physicians
may add other acupoints to alleviate additional symptoms or adjust the individual’s
constitution while managing body weight. The impact of these additional acupoints on
weight control remains unclear, as choosing specific acupoints may not be more effective
than selecting non-specific ones [58]. Nonetheless, this study demonstrates the
effectiveness of applying laser acupuncture to the most crucial acupoints for body weight
control. Further clinical studies are required to elucidate this maer fully. Finally, some
baseline demographic differences existed between the two groups. Although the PS-based
models balanced these differences, larger randomized controlled trials are necessary to
confirm the true efficacy of LA on obesity, as well as its potential side effects.
5. Conclusions
This study determined that LA may effectively reduce body weight in a real-world
seing while causing minimal adverse events or comorbidities. Compared with
liraglutide use, LA was linked to a slightly greater reduction in body weight. Owing to its
non-invasive nature, good safety profile, and lack of drug–drug interactions, it appears
promising to investigate the effects of LA alone or in combination with liraglutide in
future studies. Further large-scale clinical trials are necessary to establish the effectiveness
and safety of LA, as well as to assess the potential long-term comorbidities and adverse
events associated with this treatment.
Supplementary Materials: The following supporting information can be downloaded at:
hps://www.mdpi.com/article/10.3390/healthcare12131279/s1. Ta ble S1. Summary of acupoints
used for laser acupuncture in the present study. Table S2. Diagnostic codes used in the study. Tab l e
S3. Changes in primary endpoints and the risk of adverse events between baseline and day 180
(balanced with IPTW). Table S4. Changes in primary endpoints and the risk of adverse events
between baseline and day 180 (balanced with 1:1 PSM).
Author Contributions: Conceptualization, W.-L.Y., Y.-N.L., T.-H.Y., T.-I.K. and Y.-T.H.; data
curation, Y.-N.L., P.-W.L., C.-Y.H., J.-L.H. and Y.-T.H.; formal analysis, H.-Y.C., P.-W.L., C.-Y.H. and
J.-L.H.; funding acquisition, H.-Y.C.; investigation, T.-I.K. and J.-L.H.; methodology, W.-L.Y., Y.-N.L.,
H.-Y.C. and C.-W.Y.; project administration, Y.-N.L., H.-Y.C., T.-H. Y., C.-W.Y. and T.-I.K.; resources,
C.-Y.H.; software, H.-Y.C.; supervision, H.-Y.C. and Y.-T.H.; validation, T.-H. Y., C.-W.Y. and P.-W.L.;
visualization, W.-L.Y.; writing—original draft, W.-L.Y. and Y.-N.L.; writing—review and editing,
H.-Y.C. and Y.-T.H. All authors have read and agreed to the published version of the manuscript.
Funding: This study was funded by the Chang Gung Medical Foundation (grant number:
CMRPG1N0051), the Ministry of Health and Welfare (grant numbers: MOHW113-CMAP-M-113-

Healthcare 2024, 12, 1279 12 of 14
000003-B, MOHW113-CMAP-M-113-000002-D), and the National Science and Technology Council
in Taiwan (grant number MOST111-2320-B-182-035-MY3).
Institutional Review Board Statement: The study design and protocol were approved by the
Institutional Review Board (IRB) of the Chang Gung Medical Foundation (IRB number:
201801526B0C501, approved on 11 November 2019).
Informed Consent Statement: It was impossible to determine the identity of the subjects because
the identification numbers of the subjects were encrypted. Therefore, the requirement for informed
consent was waived by the IRB commiee.
Data Availability Statement: The data that support the findings of this study are available on
request from the corresponding author.
Acknowledgments: The authors thank Yi-Hsuan Lin for sharing her clinical expertise.
Conflicts of Interest: The authors declare no conflicts of interest.
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