Search

Importance: Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications., Objective: To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology., Design, Setting, and Participants: This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously., Interventions: Semaglutide, 2.4 mg, vs placebo., Main Outcomes and Measures: Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated., Results: This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5., Conclusions and Relevance: The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care., Trial Registration: ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).

Aim: To assess the efficacy and safety of diacerein monotherapy in adults with obesity., Methods: Forty-two adults with obesity participated in the study and were randomly assigned to receive diacerein or placebo in addition to lifestyle modification for 14 weeks, in a double-blinded fashion. Differences in changes in body weight, body composition, metabolic variables, fatty liver-related indicators, cardiovascular system variables, lifestyle score and metabolic factors were compared., Results: Post-treatment weight loss percentage from baseline was -6.56% (-8.71%, -4.41%) in the diacerein group and -0.59% (-2.74%, 1.56%) in the placebo group. Compared with the placebo group, the diacerein group showed significant improvements in body composition, metabolic variables and indicators related to fatty liver. In addition, after 14 weeks of treatment, diacerein led to a significant reduction in serum visfatin concentration versus the placebo group. The reductions in total body fat mass and visceral fat area mediated the weight loss induced by diacerein. No significant differences were found between the groups in the number of adverse events and safety variables., Conclusions: For adults with obesity, diacerein led to a clinically meaningful weight loss and provided multiple metabolic benefits with acceptable safety. These results support that diacerein is a promising candidate medicine to be developed for obesity management., (© 2024 John Wiley & Sons Ltd.)

Background & Objectives: Obesity is a common comorbidity in heart failure, yet effective pharmacological options for weight loss in these patients are limited. Semaglutide, a glucagon-like peptide 1 receptor agonist, has shown promise for weight reduction in obese adults. This study aims to evaluate semaglutide's impact on weight loss, functional status, and clinical outcomes in obese patients with heart failure., Methods: A retrospective analysis was conducted on all consecutive obese (BMI > 30 kg/m²) patients with heart failure at the University Hospital Bonn outpatient clinic from July 2019 to July 2022. Propensity score matching paired patients receiving semaglutide as an add-on therapy (SEMA) with those on medical therapy alone (Control)., Results: Among 1,942 patients with heart failure screened, 26 matched pairs were identified. At one year, the SEMA group exhibited significant weight loss, with a mean BMI reduction of -2.91 kg/m² (95% CI: -4.27 to -1.55; p < 0.001), while the control group showed a non-significant mean change of -0.41 kg/m² (95% CI: -1.08 to 0.26; p = 0.22). The difference in BMI between the two groups was statistically significant (mean difference: 3.42 kg/m², 95% CI: 1.43 to 5.42; p = 0.001). Improvements by at least one NYHA class were observed in 65% of the SEMA group (p < 0.001) compared to 15% of the control group (p = 0.18). The SEMA group also showed a significant increase in 6-minute walk distance (6MWD), with a mean difference of 75 m between the groups at one year (95% CI: 0.53 to 150.02; p = 0.049). NT-proBNP levels significantly decreased in the SEMA group (p < 0.001) compared to the control group (p = 0.78), with a statistically significant difference in NT-proBNP between the groups (p = 0.048). Both improvements in 6MWD and reductions in NT-proBNP were significantly correlated with BMI percentage reductions., Conclusions: Semaglutide was associated with significant weight reduction in obese patients with heart failure, accompanied by improved NYHA classification and 6-minute walk distance. Larger, multi-center trials and prospective, randomized controlled trials are warranted. These studies should focus on assessing long-term outcomes, optimizing dosage, and exploring the potential cardiovascular benefits beyond weight reduction., (© 2024. The Author(s).)

Aim: Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients., Methods: A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software., Results: Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient., Conclusion: Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management., (© 2024. The Author(s).)

Introdroduction: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists., Methods: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity., Results: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation., Conclusions: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background/objectives: Glucagon-like peptide-1 agonists (GLP1As) are increasingly prescribed to treat obesity. While studies document how these medications impact dietary habits, their relationship to consumer food waste is unexplored. Approximately one-third of all food is wasted, which creates substantial economic and environmental damage. The purpose of this study is to assess how consumers alter food waste after beginning GLP1As and to identify factors associated with this relationship., Methods: Retrospectively reported changes in the amount of food wasted since beginning a GLP1A are gathered from a sample of 505 U.S. consumers via a self-administered online survey. Regression analysis yields associations between changes in post-GLP1A-uptake food waste and the length and type of medication use, medication side effects, post-uptake changes in dietary habits, and respondent characteristics., Results: A total of 25% of respondents agree they waste more food since beginning the medication, while 61% disagree. Respondents are significantly less likely to agree with this statement if they have been on the medication a longer time and are significantly more likely to agree if they reported experiencing nausea since beginning the medication. Dietary changes consistent with more vegetable intake are also significantly associated with less waste., Conclusions: Uptake of a novel class of anti-obesity medications may significantly affect food waste patterns. With the potential for widespread adoption of such medications, and given the societal import of reducing food waste, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system and for equipping new GLP1A users to limit food waste.

Objective: To assess efficacy and tolerability of semaglutide as a weight loss treatment for children living with comorbid obesity., Design: Retrospective observational study of the first 50 children from a weight management service treated with semaglutide for at least 6 months., Setting: A tertiary paediatric multidisciplinary weight management clinic in a UK hospital., Patients: Aged 10-18 years old with a body mass index (BMI) SD score (SDS) >2 with a weight-related comorbidity (including insulin resistance (defined as homeostatic model assessment for insulin resistance >4), type 2 diabetes, metabolic-associated fatty liver disease, obstructive sleep apnoea or hypertension)., Interventions: Once-weekly injectable semaglutide titrated over 8 weeks to a final dose of 1 mg in addition to dietary and lifestyle advice., Main Outcome Measures: Primary outcome measures were change in weight, BMI SDS and percentage body weight. Secondary outcomes were side effects and cessation of treatment., Results: After 6 months of treatment, statistically significant decreases in BMI SDS (0.32±0.27, p<0.001) and body weight (7.03±7.50 kg, p<0.001) were seen. Mean percentage total weight loss was 6.4±6.3% (p<0.001). For the 14 patients for whom 12-month data were available, statistically significant decreases were seen in mean BMI SDS (0.54±0.52, p<0.001). Mean body weight decreased by 9.7±10.8 kg (p<0.001). Percentage total weight loss at 12 months was 8.9±10.0% (p<0.001). Mild gastrointestinal side effects were common. One patient developed gallstones. Five patients discontinued treatment due to side effects., Conclusion: Semaglutide appears to be a safe and effective weight loss adjunct when used in a multidisciplinary weight management clinic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs., Methods: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis., Results: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42-3.6). Orlistat (ROR = 3.30, 95% CI: 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45-10.88) with phentermine-topiramate still needs further clarification., Conclusions: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events., (© 2024. The Author(s).)

Semaglutide is found to be efficient for weight loss in patients with overweight or obesity with diabetes mellitus (DM). With a wide range of adverse events reported, the efficacy and safety of once-weekly subcutaneous semaglutide in individuals without DM, with overweight or obesity, is unclear. We conducted a comprehensive meta-analysis of randomized studies on once-weekly semaglutide in this patient population. We identified nine studies with 11,641 patients in the semaglutide group and 10,479 in the placebo group. We observed that semaglutide resulted in significant benefits, including change in body weight (%): mean difference (MD) of -11.49% (p < 0.0001), change in absolute body weight: MD of -11.74 kg (p < 0.0001), and change in waist circumference: MD of -9.06 cm (p < 0.0001). Gastrointestinal side effects are predominant including nausea: odds ratio (OR) of 4.06 (p < 0.0001), vomiting: OR of 4.43 (p < 0.0001), diarrhea: OR of 2.10 (p < 0.0001), constipation: OR of 2.43 (p < 0.0001), gallbladder disorders: OR of 1.26 (p = 0.010), and cholelithiasis: OR of 2.06 (p = 0.04). Serious adverse events were not statistically significant: OR of 1.06 (p = 0.82). However, the percentage of participants discontinuing due to adverse events and gastrointestinal side effects was statistically significant: ORs of 2.22 (p < 0.0001) and 3.77 (p < 0.0001), respectively. This study shows that in patients with overweight or obesity without DM, once-weekly subcutaneous semaglutide can significantly decrease body weight without risk of serious adverse events when compared with a placebo. However, gastrointestinal side effects are predominant with semaglutide, which can result in medication discontinuation., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: The prevalence of obesity has increased worldwide over the past decades. Regional variations exist in the relationship between body mass index (BMI), body fat, and health risks: Asians typically have a lower BMI than people of European descent, but a higher risk of obesity-related comorbidities. However, there is a paucity of evidence for anti-obesity medications (AOMs) in East Asian populations. In this study, we aimed to systematically review evidence regarding the safety and efficacy of AOMs among adults with obesity disease in East Asia, and to assess the feasibility of conducting an indirect treatment comparison (ITC) between the semaglutide and mazindol trials., Methods: The Embase, MEDLINE, and ICHUSHI databases were searched via the Ovid SP platform for randomized controlled trials, in English or Japanese, reporting data on semaglutide or mazindol therapy with placebo or diet and exercise as comparators. The potential risks of bias in conducting a population-adjusted ITC were determined based on the heterogeneity of potential effect modifiers and variations in study design., Results: Of 21 publications, 2 were included in this study based on the eligibility criteria. The STEP 6 study established the clinical efficacy of subcutaneous semaglutide compared with placebo in the reduction of body weight and cardiometabolic risk factors [glycated hemoglobin (HbA 1c ), total cholesterol, and systolic blood pressure] among Japanese and South Korean people with obesity disease. Mazindol also proved beneficial in reducing body weight and total cholesterol compared with placebo in Japan. Both semaglutide and mazindol were associated with higher rates of adverse events and treatment discontinuation than placebo. An ITC between the two studies was not deemed feasible based on the potential risks of bias., Conclusions: Semaglutide and mazindol are associated with significant body weight reduction among people with obesity in East Asia. Further research based on label indications and up-to-date real-world data among East Asian people with obesity would help determine additional clinical benefits., (© 2024. The Author(s).)

Competing Interests: I declare no competing interests.

Purpose of Review: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity., Recent Findings: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese., Summary: The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery., Methods: This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs., Results: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001)., Conclusion: Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment., Methods: This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%)., Results: We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m 2 ) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m 2 ). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol., Conclusions: The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Obesity and COVID-19 are at the top of nowadays health concerns with significant crosstalk between each other. The COVID-19 pandemic negatively affected healthy lifestyles and increased obesity prevalence. Thus, there was a surge in anti-obesity products (AOPs) intake. Herein, we evaluated how the pandemic has affected slimming products' efficacy and safety in patients seeking weight reduction at an urban, weight management centre in Alexandria, Egypt. In addition, the effect of AOPs on COVID-19 infection severity was also appraised to detect whether AOPs can alter COVID-19 host cell entry and infective mechanisms, and thus, affect infection severity., Methods: Patients were invited to complete an anonymous survey. The survey assessed self-reported changes in weight, the use of AOPs during the COVID-19 pandemic, COVID-19 infection severity, AOPs efficacy, and incidence of side effects. Inclusion criteria were obese patients above 18 years old who got infected by COVID-19 while receiving a single-ingredient AOP., Results: A total of 462 participants completed our anonymous validated questionnaire. Most of the participants were females (450; 98.4%) with BMI ranging from 24.98-58.46. Eligible participants were only 234 and the top-administered products were orlistat, liraglutide, metformin, green tea, cinnamon, Garcinia cambogia, and Gymnema Sylvestre. In most cases, AOPs intake was beneficial for COVID-19 infection, and most patients experienced mild-to-moderate COVID-19 symptoms. On the other hand, SARS-CoV-2 significantly interferes with AOPs' mechanisms of action which positively or negatively influences their efficacy and side effects incidence due to predictable pharmacological link., Conclusion: Concurrent AOPs intake with COVID-19 infection is a two-sided weapon; AOPs attenuate COVID-19 infection, while SARS-CoV-2 interferes with efficacy and side effects incidence of AOPs., Competing Interests: NO authors have competing interests, (Copyright: © 2024 El-Mezayen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Obesity has become a global public health concern and China has the largest number of affected people worldwide., Objective: To assess the efficacy and safety of treatment with tirzepatide for weight reduction in Chinese adults with obesity or overweight and weight-related comorbidities., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 29 centers in China from September 2021 to December 2022 included Chinese adults (aged ≥18 years) with a body mass index (BMI) greater than or equal to 28 or greater than or equal to 24 and at least 1 weight-related comorbidity, excluding diabetes., Interventions: Participants were randomly assigned (1:1:1) to receive once-weekly, subcutaneous 10-mg (n = 70) or 15-mg (n = 71) tirzepatide or placebo (n = 69), plus a lifestyle intervention, for 52 weeks., Main Outcomes and Measures: Co-primary end points were the percent change in body weight from baseline and weight reduction of at least 5% at week 52. Efficacy and safety analyses were performed on an intention-to-treat population., Results: Of 210 randomized participants (103 [49.0%] female; mean [SD] age, 36.1 [9.1] years; body weight, 91.8 [16.0] kg; BMI, 32.3 [3.8]), 201 (95.7%) completed the trial. The mean change in body weight at week 52 was -13.6% (95% CI, -15.8% to -11.4%) with tirzepatide 10 mg, -17.5% (95% CI, -19.7% to -15.3%) with tirzepatide 15 mg, and -2.3% with placebo (difference between 10 mg and placebo, -11.3% [95% CI, -14.3% to -8.3%; P < .001]; difference between 15 mg and placebo, -15.1% [95% CI, -18.2% to -12.1%; P < .001]). The percentage of participants achieving body weight reductions of 5% or greater was 87.7% with tirzepatide 10 mg, 85.8% with tirzepatide 15 mg, and 29.3% with placebo (P < .001 for comparisons with placebo). The most frequent treatment-emergent adverse events with tirzepatide were gastrointestinal. Most were mild to moderate in severity, with few events leading to treatment discontinuation (<5%)., Conclusions and Relevance: In Chinese adults with obesity or overweight, once-weekly treatment with tirzepatide 10 mg or 15 mg resulted in statistically significant and clinically meaningful weight reduction with an acceptable safety profile., Trial Registration: ClinicalTrials.gov Identifier: NCT05024032.

Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia., Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16 964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants)., Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.

Competing Interests: Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Background: Obesity has been established as a significant risk factor for osteoarthritis. Anti-obesity medications (AOMs) have demonstrated efficacy in weight management. However, potential impact on osteoarthritis risk remains uncertain., Methods: This retrospective cohort study used Kythera data from NOV2022 to JULY2024. Patients with obesity using AOMs were identified through diagnosis and prescription claims for tirzepatide, semaglutide, or liraglutide between 1NOV2023 and 31JAN2024, with a 6-month follow-up to assess OA risk. OA risk, analyzed using Cox regression and propensity score matching, controlled for comorbidities and sociodemographic factors., Results: There were 39,394 patients living with obesity using AOM (23,933 semaglutide 12,854 tirzepatide, 2,607 liraglutide) and 72,405 without AOM use. The adjusted osteoarthritis risk was 27% % lower in AOM users than in non-users (hazard ratio (HR) = 073, 95% CI (0.67-0.79), p  < 0.01). Among AOMs, tirzepatide was associated with a significantly lower osteoarthritis (OA) risk compared to semaglutide (HR = 0.57, 95% CI: 0.50-0.65, p  < 0.0001). Liraglutide was linked to a significantly higher OA risk vs tirzepatide (HR = 1.63, 95% CI: 1.23-2.15, p  = 0.0007)., Conclusions: AOM use was associated with a significantly lower risk of OA and may be an effective obesity management intervention.

Purpose of Review: The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use., Recent Findings: Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. As of this review, only one large randomized clinical trial of semaglutide in youth has been completed, with a follow-up duration of 68 weeks. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Due to the cost of semaglutide, particularly in the United States, limited cost effectiveness analyses have demonstrated unfavorable incremental cost-effectiveness ratios for semaglutide relative to phentermine-topiramate as an alternative antiobesity medication in adolescents., Summary: Semaglutide represents an important advance in the pediatric obesity management, with clear short-term reductions in BMI and improvement in metabolic parameters. However, its long-term safety and efficacy for youth with obesity remain to be demonstrated. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The most successful obesity therapeutics, glucagon-like peptide-1 receptor (GLP1R) agonists, cause aversive responses such as nausea and vomiting 1,2 , effects that may contribute to their efficacy. Here, we investigated the brain circuits that link satiety to aversion, and unexpectedly discovered that the neural circuits mediating these effects are functionally separable. Systematic investigation across drug-accessible GLP1R populations revealed that only hindbrain neurons are required for the efficacy of GLP1-based obesity drugs. In vivo two-photon imaging of hindbrain GLP1R neurons demonstrated that most neurons are tuned to either nutritive or aversive stimuli, but not both. Furthermore, simultaneous imaging of hindbrain subregions indicated that area postrema (AP) GLP1R neurons are broadly responsive, whereas nucleus of the solitary tract (NTS) GLP1R neurons are biased towards nutritive stimuli. Strikingly, separate manipulation of these populations demonstrated that activation of NTS GLP1R neurons triggers satiety in the absence of aversion, whereas activation of AP GLP1R neurons triggers strong aversion with food intake reduction. Anatomical and behavioural analyses revealed that NTS GLP1R and AP GLP1R neurons send projections to different downstream brain regions to drive satiety and aversion, respectively. Importantly, GLP1R agonists reduce food intake even when the aversion pathway is inhibited. Overall, these findings highlight NTS GLP1R neurons as a population that could be selectively targeted to promote weight loss while avoiding the adverse side effects that limit treatment adherence., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Goals: We aim to describe the weight loss outcomes of patients with celiac disease (CeD) taking antiobesity medications (AOMs) and compare it with the weight loss outcomes of patients without CeD taking AOMs., Background: Increasing rates of obesity and obesity-associated comorbidities have been previously reported in patients with CeD on a gluten-free diet. The effectiveness of AOMs in this population has not been previously described., Methods: In our retrospective cohort study, we matched 39 patients with treated CeD to 78 patients without CeD based on sex and AOM. We assessed the weight loss outcomes at 3, 6, and 12 months after starting the AOM in both cohorts and analyzed if there was a differential response when comparing by type of AOM [injectable glucagon-like peptide 1 (GLP-1) receptor agonists vs. oral non-GLP-1 AOMs]., Results: Both cohorts had similar baseline demographic and anthropometric characteristics. At 12 months, the CeD cohort had a nonsignificantly inferior total body weight loss percentage compared with the cohort without CeD (6.5% vs. 9.5%, P =0.13). The CeD cohort had a similar proportion of patients achieving a total body weight loss percentage of ≥5% than the cohort without CeD (72.7% vs. 72.1%, P =1.00). No significant difference was observed when comparing the weight loss outcomes of injectables (GLP-1 receptor agonists) to oral AOMs. The proportion of patients reporting side effects was similar for both groups, regardless of the type of AOM., Conclusion: Patients with CeD taking AOMs had similar weight loss outcomes to patients without CeD. Hence, AOMs can be a safe and effective therapy for weight management in patients with CeD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The objective of this narrative review is to advocate for improved comprehensive care of patients with obesity and infertility. Persons with an increased body mass index have less successful reproductive outcomes, and recently, new medications to treat neuroendocrine hormone imbalances are producing meaningful weight loss akin to surgical interventions. For the first time, obesity is publicly being recognized as a disease. These medications contain the newest generation of glucagon-like peptide 1 receptor agonists and deserve our attention for several reasons: regardless of body mass index, many patients will be using them; it is necessary to understand the mode of action, side effects, and implications for anesthetic procedures and pregnancy; and it is important to evaluate when they could be used to improve health outcomes and/or access to fertility care., Competing Interests: Declaration of Interests A.S.G. reports honoraria from Biosyent. C.E.B. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism., Methods: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8., Results: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group., Conclusions: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients., Trial Registration: ClinicalTrials.gov NCT03451734., (© 2024. The Author(s).)

Importance: Body mass index (BMI) of the 95th or greater percentile for age and sex is common among young people, and its prevalence has increased in recent decades., Objective: To examine the benefits and harms of weight management interventions initiated in health care settings among children and adolescents with high BMI., Data Sources: MEDLINE via Ovid, PsycINFO via Ovid, and the Cochrane Central Registry of Controlled Trials through January 12, 2023; ongoing surveillance through January 26, 2024., Study Selection: English-language studies of weight management interventions (behavioral and pharmacologic, including liraglutide, semaglutide, orlistat, and phentermine/topiramate) among children aged 2 to 18 years with high BMI (eg, ≥85th or ≥95th percentile for age and sex) conducted in or recruited from health care settings., Data Extraction and Synthesis: One investigator abstracted data; a second checked for accuracy. Outcomes with sufficient evidence for meta-analysis were pooled using random-effects models., Main Outcomes and Measures: BMI and other weight-related outcomes, cardiometabolic measures, quality of life, physical activity, dietary pattern scores, and harms., Results: Fifty-eight randomized clinical trials (RCTs) were included (N = 10 143). Behavioral interventions were associated with small reductions in BMI and other weight outcomes after 6 to 12 months (28 RCTs [n = 4494]; mean difference in change between groups, -0.7 [95% CI, -1.0 to -0.3]). Larger effects were seen in interventions with higher contact hours and that offered physical activity sessions. Reporting was sparse for outcomes other than BMI, with few significant findings. Semaglutide and phentermine/topiramate had the largest effects on BMI (eg, 1 RCT [n = 201] for semaglutide; mean difference, -6.0 [95% CI, -7.3 to -4.6]). The very few studies that evaluated outcomes after medication discontinuation showed immediate weight regain. Gastrointestinal adverse effects were common with liraglutide, semaglutide, and orlistat. Serious adverse effects were rare, but no studies had follow-up longer than 17 months., Conclusions and Relevance: In the short term, weight management interventions led to lower BMI in children and adolescents, with no evidence of serious harm. Evidence is lacking about how weight management interventions affect BMI beyond 1 year and after medication discontinuation and about longer-term effects on other outcomes.

Targeting the cannabinoid type 1 receptor (CB1) is a clinically validated antiobesity therapeutic approach. The only such drug approved, rimonabant, was launched in 2006 in Europe but subsequently rejected by the US Food and Drug Administration (FDA) in 2007. The FDA cited the increased risk of suicidality in its opposition to rimonabant's approval, leading to the drug's eventual worldwide withdrawal and the abandonment of this class of therapeutics. Seventeen years later, a new class of CB1-targeting drugs is emerging, but the impact of the 2007 FDA decision remains a formidable obstacle to its clinical development. We revisit the suicidality data presented by the FDA in light of the evolution of suicidality assessment and cross-reference this with the data in the subsequently published clinical trials. We conclude that the publicly available data do not support the FDA's conclusion that the use of rimonabant was associated with an increase in the risk of suicidality., (© 2024 Corbus Pharmaceuticals, Inc. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objective: Obesity and its cardiovascular complications are major causes of morbidity and mortality. Little is known in real-world settings about the effect of newly approved antiobesity medications (AOMs) on cardiovascular complications among patients with obesity., Methods: This retrospective cohort study examined the association between newly approved AOM use and cardiovascular events among Medicare patients with obesity using data from 2020 to 2022. Patient age, gender, comorbidity scores, socioeconomic status, and baseline cardiovascular comorbidities were compared descriptively. Subgroup analysis compared variables by medication type. Relative risk and absolute risk of cardiovascular disease (CVD) events were estimated using Cox and Aalen regression models., Results: The analysis included 5926 patients treated with semaglutide and tirzepatide, including Ozempic (5404 patients), Wegovy (375 patients), or Mounjaro (147 patients). Hypertension, type 2 diabetes, and hyperlipidemia were the most common comorbidities. For patients with AOMs, less incidence of heart failure (4.89% vs. 6.13%, p < 0.0001), atrial fibrillation (3.83% vs. 5.17%, p < 0.0001), arrhythmia (3.59% vs. 4.14%, p < 0.0153), and peripheral vascular disease (3.44% vs. 2.94%, p < 0.0395) was found versus patients without AOMs. Patients receiving AOMs showed an 8% risk reduction in any CVD. Protective effect on CVD was apparent over the first 375 days., Conclusions: Results suggest that utilization of AOMs effectively alleviates the high prevalence of CVD., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objective: The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials., Methods: The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo., Results: Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups., Conclusions: The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

We present a case of a case of a man in his 70s on multiple medications (including treatment of ischemic heart disease and diabetes who developed significant rhabdomyolysis, complicated by acute kidney injury (AKI) and encephalopathy, while using a compounded medication for weight loss. The patient was admitted to the intensive care unit and progressed favourably after haemodialysis and supportive care. Information regarding the ingestion of weight-loss drugs was unknown at the time of admission and was only discovered after resolution of encephalopathy, raising the possibility of toxin-associated rhabdomyolysis. This case emphasises the need for a thorough clinical history and scrutiny of the safety of weight-loss prescriptions, including preparations that comprise a combination of drugs and supplements that may adversely interact with chronic medications, especially in polymedicated patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Semaglutide is the second marketed glucagon-like peptide 1 receptor agonist that can be used safely and efficiently in non-diabetic people with excess weight, providing a new milestone in the pharmacological treatment of obesity. This narrative review aims to describe the clinical actions of this new drug in weight management in non-diabetic patients along with possible side-effects and dropout reasons. To accomplish this, the PubMed database was searched to retrieve the most relevant clinical studies published to date on this topic, using the following keywords "semaglutide and obesity". Currently, semaglutide is on the market in two formulations, the once-weekly subcutaneous (s.c.) semaglutide and once-daily oral semaglutide. Data in the literature on the anti-obesity action of semaglutide are available for both routes of administration of the drug, with a prevalence of studies using the s.c. one. However, given its dosage, oral semaglutide may provide greater attractiveness and better treatment adherence, but further research is needed in this field.

Introduction: The use of natural products for therapeutic purposes is a common practice throughout the world, in part, due to the global obesity epidemic and the search for products with appetite suppression and weight loss properties, which include nutritional supplements, vitamins and minerals to herbal products. It is known that such products may be associated with various adverse health effects. Thus, the objective of this study is to report a series of cases of patients, who presented fulminant liver failure (HFI) requiring liver transplantation (LT), related to the consumption of products used for weight loss., Material and Methods: This is a retrospective cohort based on the evaluation of patients listed for LT due to IHF at the Hospital das Clínicas of the Universidade Estadual de Campinas, between 1991 and 2022, with patients who had confirmed consumption of products with the aim of loss being selected., Results: During the studied period, 92 patients were listed for HT due to IHF according to the Kings College criteria, with 5 cases being selected with proven consumption of herbal products for weight loss, and other causes that could explain the IHF were excluded. Four (80%) of the patients were female, with a mean age of 40.5 years, and 40% of the cases died., Discussion and Conclusions: Unlike traditional pharmaceutical medicines, in most countries, the commercialization of these products is not conditioned on clinical and safety evidence or prior approval by regulatory bodies. Hepatoxicity can be related to several factors, such as the presence of toxins naturally found in plants, the presence of heavy metals, contamination during obtaining or processing and the addition of substances omitted from the labels. The use of weight loss products can evolve with IHF, a fact that deserves attention, due to ease of access and growing demand, and it is important to regulate the trade of these products and raise public awareness about the risks of use without professional supervision and guidance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To compare weight loss outcomes between patients starting semaglutide who had previously been on another anti-obesity medication (AOM) compared to those who were AOM-naïve., Materials and Methods: We performed a retrospective study in patients with overweight or obesity taking semaglutide for weight loss for a duration of 3 to 12 months. Our primary endpoint was assessment of percentage of total body weight loss (TBWL) in patients who started semaglutide as their first AOM (AOM-naïve) compared to those who started semaglutide and had previously taken another AOM (non-AOM-naïve). The secondary outcome was a comparison of the proportions of patients achieving ≥5%, ≥10%, ≥15% and ≥20% TBWL between the groups. Our endpoints were analysed using independent t-tests and ANOVA/ANCOVA for continuous variables and Pearson's test for categorical variables., Results: This study included 305 patients. Outcomes of semaglutide treatment were superior in AOM-naïve patients (n = 231) compared to non-AOM-naïve patients (n = 74) at 3 (6.3% vs. 3.8%), 6 (10.6% vs. 6.7%), 9 (14.0% vs. 9.1%) and 12 months (14.3% vs. 10.6%; p < 0.0001 at 3, 6 and 9 months, and p = 0.01 at 12 months). A greater proportion of patients in the AOM-naïve group achieved a TBWL ≥ 15% (48% vs 21%; p = 0.02) and ≥20% (27% vs 4% p < 0.01) at 12 months., Conclusion: The use of semaglutide in patients with previous intake of other AOMs was associated with inferior weight loss outcomes in comparison to patients who were AOM-naïve., (© 2024 John Wiley & Sons Ltd.)

Background: The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes., Methods: For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023., Results: Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)]., Conclusions: In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)