INTRODUCTION
The prevalence of overweight and obesity has been rising rapidly worldwide, including in South Korea. 1 , 2 Obesity significantly increases the risk of numerous comorbidities, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and obesity-related cancers. 3 - 5 As a result, timely diagnosis and effective management of obesity are now essential components of routine clinical practice.
To address this growing public health challenge, the Korean Society for the Study of Obesity (KSSO) has developed the 9th edition of its Clinical Practice Guidelines for Obesity. 6 These guidelines are designed to assist clinicians, particularly those in primary care, in making evidence-based decisions to optimize both the safety and efficacy of obesity management. Each recommendation is accompanied by clearly defined levels of evidence and anticipated clinical benefits, with rigorous evaluation to prevent ineffective or potentially harmful interventions. Major updates in the 9th edition include the explicit recognition of ‘obesity as a disease,’ underscoring its status as a chronic, relapsing medical condition; the introduction of pharmacologic agents newly approved by the Ministry of Food and Drug Safety; and the incorporation of recent scientific evidence to ensure that recommendations are both current and comprehensive. The guidelines also include a newly added section on health functional foods, a regulatory category unique to South Korea.
This article summarizes the key clinical questions addressed in the guidelines, with a particular focus on diagnosis and pharmacotherapy. In addition, it outlines the methodology used to develop the recommendations and presents the rationale underlying each recommendation.
METHODS
Guideline development process
To evaluate the previous edition and identify areas in need of revision, a structured survey was administered to members of the Committee of Clinical Practice Guidelines and the executive board of the KSSO. The topics included in the 9th edition were selected based on the survey results and expert consensus. The updated guidelines were developed using the adaptation methodology outlined in manuals published by the Ministry of Health and Welfare of South Korea and the Korean Academy of Medical Sciences. 7
Committee formation and roles
Given the interprofessional nature of obesity management, the KSSO convened a diverse committee comprising medical specialists (family physicians, endocrinologists, pediatricians, general surgeons, and psychiatrists), clinical nutritionists, and exercise professionals. A steering board of seven members, including the director and secretary of the Committee of Clinical Practice Guidelines, was established to oversee the development process, with major decisions made by consensus.
All committee members received formal training in clinical practice guideline development, including the formulation of key clinical questions and the conduct of systematic literature reviews. Drafted recommendations were prepared by committee members according to their respective clinical or research expertise, with topics assigned according to each member’s specialty to ensure comprehensive and expert-driven content.
Formulation of key questions
Key clinical questions were formulated using the Population, Intervention, Comparison, and Outcome framework. 8 This structured approach enabled the systematic evaluation of treatment alternatives by clearly defining target populations and relevant clinical context.
Systematic literature review
A systematic literature search was conducted by two trained information specialists. For each topic, tailored search strategies were developed and applied to both international and national databases: PubMed, Embase, the Cochrane Library, KoreaMed, the Research Information Sharing Service, and ScienceON. The following guideline repositories were reviewed: Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, and National Health and Medical Research Council. Supplementary searches were performed using Google. All searches included publications from January 2014 through May 2023.
Eligible sources comprised randomized controlled trials (RCTs), cohort studies, systematic reviews, meta-analyses, and existing clinical guidelines. Narrative reviews were also included when RCT evidence was insufficient for specific topics.
Class of recommendation and level of evidence
The strength and quality of each recommendation were assessed using the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. 9 The Class of Recommendation indicates the strength of each recommendation, determined by evaluating the level of evidence, the balance of benefits and risks, feasibility, acceptability, and applicability, particularly in primary care settings. Recommendations are categorized into four classes (I, IIa, IIb, and III), as summarized in Table 1 .
Table 1
Definitions of classes of recommendation and levels of evidence
Recommendations were categorized by strength (Class I–III) and level of evidence (A–D), as defined according to the Grading of Recommendations Assessment, Development and Evaluation framework.
| Category | Definition |
| Class of recommendation | |
| Class I (Is recommended) | A strong recommendation based on high-quality evidence (Level A), with clear clinical benefit and broad applicability |
| Class IIa (Should be considered) | A moderate-strength recommendation supported by moderate-quality evidence (Level B), with likely clinical benefit and reasonable applicability |
| Class IIb (May be considered) | A weak recommendation supported by low- to very low-quality evidence (Level C or D); clinical benefit is uncertain, but applicability is moderate to high |
| Class III (Is not recommended) | A recommendation against use due to potential harm or lack of benefit, limited applicability, typically supported by low-quality evidence (Level C or D) |
| Level of evidence | |
| Level A | High-quality evidence derived from multiple randomized controlled trials, meta-analyses, or systematic reviews |
| Level B | Evidence from well-designed nonrandomized studies, including cohort or case-control studies |
| Level C | Evidence from observational studies or case series, with limited methodological rigor |
| Level D | Consensus-based recommendations derived from expert opinion or clinical experience in the absence of direct supporting evidence |
For recommendations supported by a low level of evidence but judged to offer clear benefits or high practical applicability, the committee reached consensus to upgrade the class of recommendation. Applicability in clinical settings was determined through discussions among steering committee members and authors, with particular emphasis on practical utility for primary care physicians.
The level of evidence represents the quality and reliability of the supporting scientific data, assessed according to the type, quantity, and consistency of evidence from clinical trials and other relevant sources. Levels of evidence are classified into four grades (A, B, C, and D) ( Table 1 ).
SUMMARY OF KEY QUESTIONS AND RECOMMENDATIONS
The 9th edition of the Clinical Practice Guidelines addresses 51 key questions across 15 topics and presents 66 recommendations ( Supplementary Table 1 ). 6 Several significant updates have been made to the 8th edition. 10 , 11 First, the concept of ‘clinical obesity,’ defined as excess adiposity accompanied by organ dysfunction or impaired daily activities, has been newly introduced. This reflects a shift from body mass index (BMI)-centric definitions to those emphasizing functional alterations at the level of tissues, organs, and the whole individual. Second, the BMI thresholds for initiating pharmacotherapy have been revised to reflect population-specific risk profiles in South Korea. Pharmacotherapy is now recommended for individuals with a BMI ≥25 kg/m 2 or a BMI ≥23 kg/m 2 in the presence of obesity-related comorbidities. Third, the guidelines incorporate newly approved obesity management medications (OMMs), including semaglutide 2.4 mg and tirzepatide, based on evidence from recent clinical trials. Fourth, a new section on health functional foods has been added to reflect growing public interest in them and address the need to critically evaluate their efficacy, safety, and regulatory limitations.
These updates reinforce that obesity is a chronic, relapsing disease and underscore that the primary goal of treatment is not simply weight reduction, but the improvement of obesity-related health outcomes.
DIAGNOSTIC CRITERIA FOR OBESITY
The definition of obesity in the updated guidelines remains consistent with the 8th edition. 10 Diagnosis is primarily based on BMI for adults and BMI percentiles for children and adolescents. Although BMI remains the most widely used metric for defining obesity and determining treatment thresholds, it does not fully capture individual metabolic risk. Therefore, the guidelines now incorporate body fat mass assessment and introduce the novel concept of clinical obesity, which was not included in previous editions.
The diagnosis of obesity requires the confirmation of excess adiposity using at least one anthropometric criterion (e.g., waist circumference) or direct measurement of body fat, in addition to BMI. In accordance with the Lancet Diabetes & Endocrinology Commission, 12 confirmation of obesity status indicates the presence of excess fat mass but does not, in itself, constitute a disease diagnosis. Individuals with confirmed obesity should subsequently be evaluated for clinical obesity, which is defined as excess adiposity accompanied by organ dysfunction, metabolic abnormalities, or functional impairments, regardless of BMI. This assessment should be based on medical history, physical examination, and standard laboratory or other diagnostic tests, following the detailed criteria provided in Table 2 .
Table 2
Assessment for obesity-related comorbidities
HDL, high-density lipoprotein; LDL, low-density lipoprotein; HbA1c, glycosylated hemoglobin.
| System | Obesity-related comorbidities | Laboratory or other diagnostic tests |
| Cardiovascular system | Hypertension, atherosclerotic cardiovascular disease, heart failure, venous thromboembolism (deep vein thrombosis and pulmonary embolism), and varicose veins | Blood pressure, pulse, and electrocardiogram; further evaluation as indicated (e.g., echocardiography and stress test) |
| Gastrointestinal system | Metabolic dysfunction-associated steatotic liver disease, gallstones, gastroesophageal reflux, and hernia | Liver function tests; abdominal ultrasound, endoscopy, or additional work-up, as indicated (e.g., fibrosis-4 index) |
| Respiratory system | Hypoventilation, asthma, and obstructive sleep apnea | Chest X-ray, pulmonary function tests, neck circumference, and polysomnography, as indicated |
| Endocrine system | Insulin resistance, metabolic syndrome, type 2 diabetes mellitus, dyslipidemia, hyperuricemia, or gout | Fasting glucose, lipid profile (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol), uric acid, HbA1c, and fasting insulin, as indicated |
| Genitourinary system | Hypogonadism, stress incontinence, chronic kidney disease, and nephrolithiasis Women: Oligomenorrhea, anovulation, polycystic ovary syndrome, precocious puberty, infertility, pregnancy complications, and birth defects Men: Erectile dysfunction and gynecomastia | Further evaluation as indicated |
| Musculoskeletal system | Limitations of mobility, back and limb pain, osteoarthritis, spinal diseases, and foot problems | Further evaluation as indicated |
| Neurologic system | Idiopathic intracranial hypertension, headache, stroke, cognitive impairment, dementia, and meralgia paresthetica | Further evaluation as indicated |
| Psychological | Depression, anxiety, low self-esteem, eating disorders, decreased work performance, reduced quality of life, and body dissatisfaction | Further evaluation as indicated |
| Cancer | Esophagus, stomach, colon and rectum, liver, pancreas, gallbladder, kidneys, thyroid, breast (postmenopausal), ovaries, uterus, meningioma, and multiple myeloma | Further evaluation as indicated |
| Other | Acanthosis nigricans, skin infection, periodontal disease, and lymphedema | Further evaluation as indicated |
The guidelines also define preclinical obesity as a state of excessive fat accumulation in which tissue and organ function is preserved. If this state persists, it could progress to clinical obesity, increasing the risk of chronic conditions such as cardiometabolic diseases and cancers. 6
This two-step approach enhances the practical applicability of the guidelines and ensures that both excess adiposity and its clinical consequences are appropriately identified and addressed. However, we acknowledge that these criteria are currently based on expert consensus and require further validation before widespread adoption. Additional research is needed to determine whether this approach can ultimately improve health outcomes.
PHARMACOLOGICAL TREATMENT
Identifying candidates for obesity pharmacotherapies
Because obesity is a chronic disease, treatment decisions should no longer rely exclusively on traditional BMI thresholds. Recent evidence increasingly supports the concept of clinical obesity. 12 This paradigm shift is particularly relevant in the era of newly available OMMs, which have demonstrated substantial weight reduction, as well as clinically significant improvements in cardiometabolic health. 13 Therefore, pharmacotherapy should be considered based on an individual’s overall metabolic risk and obesity-related health burden, rather than BMI alone.
Key questions and recommendations
Question 1. Is pharmacologic treatment more effective than lifestyle intervention alone for achieving weight loss in people with overweight or obesity?
Question 2. Is pharmacologic treatment more effective than lifestyle intervention alone for maintaining weight loss in people with overweight or obesity?
| Recommendation 1. Lifestyle modification, including dietary intervention, physical activity, and behavioral therapy, remains the cornerstone of obesity management. Pharmacologic treatment should be used as an adjunct to these interventions. (Class I, Level A) |
Rationale
Lifestyle modification directly targets the fundamental mechanisms underlying weight gain and therefore remains the primary strategy for obesity management. 14 However, physiological compensatory responses often undermine sustained weight loss. Reductions in energy intake or increases in energy expenditure typically trigger increased appetite and decreased metabolic rate, limiting the long-term success of lifestyle interventions and making it difficult to achieve and maintain clinically meaningful (5% to 10%) weight loss. 15
OMMs help mitigate the compensatory adaptations by influencing appetite regulation and energy homeostasis. 14 Clinical trials consistently demonstrate greater weight reductions when OMMs are combined with lifestyle interventions, compared with lifestyle interventions alone. Most long-term studies have evaluated pharmacotherapy in conjunction with dietary and behavioral changes, and they consistently show significantly enhanced weight-loss outcomes with pharmacotherapy ( Table 3 ). However, evidence about the efficacy of pharmacotherapy in the absence of lifestyle intervention remains limited. Intensive behavioral therapy appears to amplify the effects of certain medications, but efficacy varies by pharmacologic agent. For instance, clinical trials of naltrexone sustained-release (SR)/bupropion SR have demonstrated greater weight reduction when they are combined with intensive behavioral therapy. 16 In contrast, studies of liraglutide 3.0 mg and semaglutide 2.4 mg have not clearly shown that intensive behavioral therapy has additional benefits beyond standard lifestyle interventions. 17 , 18
Table 3
Key clinical trials of long-term pharmacologic treatments for obesity
Based on current evidence, the KSSO recommends pharmacologic treatment as an adjunct to lifestyle intervention for individuals with overweight or obesity who have not achieved adequate weight loss through non-pharmacologic interventions. With recent advances in OMMs capable of inducing substantial (>10%) weight reductions, optimizing the timing of pharmacotherapy initiation has become an important clinical consideration. A key question remains whether pharmacotherapy should be introduced only after unsuccessful lifestyle interventions or initiated concurrently with them. For example, the 2015 Endocrine Society guidelines recommended introducing pharmacotherapy following unsuccessful lifestyle intervention, 19 whereas the 2020 Obesity Canada guidelines (updated in 2022) advocate for concurrent initiation. 20 These differing approaches reflect ongoing uncertainty regarding the optimal integration of pharmacotherapy into obesity management. Further research is warranted to clarify the best timing and conditions for initiating OMMs.
| Recommendation 2. Pharmacologic treatment may be considered for adults with a BMI ≥25 kg/m² who have not achieved sufficient weight loss with dietary intervention, physical activity, and behavioral therapy alone. (Class IIa, Level B) |
Rationale
International guidelines traditionally recommend initiating pharmacotherapy at a BMI ≥30 kg/m 2 , or ≥27 kg/m 2 in the presence of obesity-related comorbidities. Those thresholds, derived from U.S. Food and Drug Administration (FDA) labeling, have been widely endorsed by major organizations, including the American Heart Association/American College of Cardiology/The Obesity Society, the Endocrine Society, and Obesity Canada. 19 - 21 The American Association of Clinical Endocrinologists further recommends individualized treatment decisions based on the severity of obesity-related complications. 22
However, Asian populations, including Koreans, experience increased obesity-related health risks at lower BMI thresholds. 23 Accordingly, the KSSO recommends considering pharmacologic treatment at a BMI ≥25 kg/m 2 and at a BMI ≥23 kg/m 2 in the presence of an obesity-related comorbidity such as T2DM, hypertension, dyslipidemia, CVD, metabolic dysfunction-associated steatotic liver disease (MASLD), obstructive sleep apnea (OSA), polycystic ovary syndrome, or osteoarthritis. This recommendation reflects growing evidence that metabolic dysfunction and related complications can occur below traditional BMI thresholds in Asian populations. 24 Given those broad eligibility criteria, clinicians should carefully weigh the potential benefits and risks, particularly for individuals with a BMI of 23 to 25 kg/m 2 and those who are metabolically healthy. Treatment decisions should be guided by a comprehensive assessment of overall health risk, consistent with the concept of clinical obesity.
As highly effective OMMs become increasingly available, it is critical to adopt clinical criteria that incorporate metabolic and functional assessments to optimize health outcomes. To ensure safe and appropriate use, we recommend an early evaluation of treatment response and regular follow-up every 3–6 months to monitor weight, metabolic parameters, and adverse effects, with ongoing reassessment of the indication for pharmacotherapy.
Question 3. Are approved OMMs effective for initiating weight loss and sustaining long-term weight management?
| Recommendation 3. Pharmacologic treatments with proven efficacy and safety in large-scale clinical trials should be used to induce initial weight loss and support long-term weight management. (Class I, Level A) |
Rationale
The primary objective of pharmacotherapy for overweight or obesity is to achieve sustained weight loss and metabolic improvement, rather than transient reductions that are difficult to maintain. Clinical trials have consistently demonstrated that pharmacotherapy facilitates long-term weight maintenance more effectively than lifestyle intervention alone ( Table 3 ). 16 , 18 , 25 - 43 Weight loss induced by OMMs typically follows a biphasic pattern, with the greatest reduction observed within the first 3–6 months, followed by a plateau. 25 , 26 , 44 Discontinuation of pharmacologic treatment commonly results in weight regain, highlighting the chronic and relapsing nature of obesity and the need for ongoing management. 27 , 28
As of 2024, several medications approved in South Korea for chronic obesity management have demonstrated robust efficacy and safety profiles in large-scale clinical trials: orlistat, naltrexone SR/bupropion SR, phentermine/topiramate extended-release (ER), liraglutide 3.0 mg, semaglutide 2.4 mg, and tirzepatide (pending launch).
Orlistat
Orlistat reduces dietary fat absorption by approximately 30% by inhibiting gastrointestinal lipases, resulting in weight loss primarily via decreased energy intake. 45 Unlike centrally acting agents, orlistat does not directly modulate appetite, and it is associated with gastrointestinal adverse effects such as steatorrhea and fecal incontinence. 46
Naltrexone SR/Bupropion SR
The combination of naltrexone SR and bupropion SR modulates appetite centrally through hypothalamic and reward pathways. Bupropion enhances dopaminergic signaling within the mesolimbic system, thereby reducing cravings and hedonic eating. 47 Naltrexone sustains anorexigenic signaling by blocking opioid-mediated inhibition of proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons and by modulating the nucleus accumbens pathways. 48 , 49
Phentermine/Topiramate ER
Phentermine/topiramate ER exerts synergistic anorectic effects through sympathomimetic and γ-aminobutyric acid (GABA)ergic mechanisms. Phentermine stimulates norepinephrine signaling, promoting satiety and increasing energy expenditure, 50 whereas topiramate enhances GABA signaling and suppresses agouti-related protein/neuropeptide Y neurons, thereby reducing appetite and cravings. This combination targets both central appetite regulation and the cognitive and emotional drivers of eating behavior. 51 , 52
Liraglutide 3.0 mg and Semaglutide 2.4 mg
Glucagon-like peptide-1 (GLP-1) receptor agonists promote weight loss by suppressing appetite, delaying gastric emptying, and enhancing satiety signaling. 53 - 55 These agents also influence gut–brain communication, modifying food preferences and reducing overall energy intake. 56 , 57 Semaglutide 2.4 mg has demonstrated greater weight loss efficacy than liraglutide (3.0 mg), likely due to its higher receptor affinity, longer half-life, and more pronounced effects on food cravings and eating behavior. 54 , 58 , 59
Tirzepatide
Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, induces substantial weight loss through complementary metabolic pathways. 60 , 61 It has demonstrated superior efficacy in weight reduction than GLP-1 receptor agonists alone while maintaining a comparable adverse event profile. 62 , 63 Although GIP is traditionally recognized for its insulinotropic effects, emerging evidence suggests that it also influences adipose tissue metabolism and enhances satiety. 64 Nevertheless, the underlying mechanisms remain incompletely understood, warranting further research to clarify the distinct contributions of GIP and GLP-1 receptor activation.
| Recommendation 4. If an individual fails to achieve ≥5% weight loss within 3 months of reaching the maintenance dose of an OMM, the medication should be discontinued or switched. (Class I, Level A) |
Rationale
The effectiveness of OMMs varies depending on the specific pharmacologic agent, treatment adherence, concurrent lifestyle interventions, and the presence of comorbidities. Clinical trial evidence indicates that individuals who do not achieve ≥5% weight loss within 12 weeks on a maintenance dose of an OMM are unlikely to derive significant benefit from continued treatment. 65 - 67 Thus, the 12-week threshold serves as a practical marker for distinguishing responders from non-responders. 65 Discontinuing or switching medications in non-responders is critical to optimize treatment outcomes, minimize unnecessary medication exposure, reduce adverse events, and control healthcare costs. Transitioning to an alternative agent with a different mechanism of action might improve the likelihood of achieving clinically significant weight loss.
In addition, short-term appetite suppressants, such as phentermine, diethylpropion, and phendimetrazine, are approved in South Korea for use up to 3 months. These centrally acting agents suppress appetite by promoting norepinephrine release. 46 Given their stimulant properties, they should not be combined with other weight-loss medications and should be prescribed with caution, particularly in individuals with cardiovascular risk factors or a history of substance use disorder. 46
Question 4. Are specific pharmacologic treatments preferred for obesity management in people with obesity-related health conditions?
Rationale
Obesity management should be individualized, particularly in the presence of obesity-related comorbidities. Certain OMMs provide additional benefits for conditions such as T2DM, atherosclerotic cardiovascular disease (ASCVD), heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction-associated steatohepatitis (MASH), and OSA. The selection of a pharmacologic treatment should account for those factors to improve overall health outcomes.
T2DM and prediabetes
In people with overweight or obesity and T2DM, all approved OMMs can be considered unless contraindicated. Incretin-based therapies, originally developed for T2DM, exhibit potent glucose-lowering effects. RCTs demonstrate that liraglutide 3.0 mg improves glycemic control in individuals with obesity and T2DM. 29 Semaglutide 2.4 mg lowered glycosylated hemoglobin levels to below 6.5% in 67.5% of participants with overweight or obesity and T2DM. 30 In East Asian populations, those agents also improve visceral adiposity and metabolic parameters. 31 , 32 Furthermore, GLP-1 receptor agonists reduce the risk of cardiovascular and kidney outcomes, 68 providing significant clinical advantages for this population.
OMMs also contribute to diabetes prevention. In a 3-year study, liraglutide 3.0 mg delayed the onset of T2DM and reduced progression by 79%. 69 Semaglutide 2.4 mg restored normoglycemia in 84.1% to 89.5% of individuals with overweight or obesity and prediabetes. 18 , 27 , 33 More recently, tirzepatide has demonstrated even greater efficacy in both obesity management and diabetes prevention. In a 176-week study, tirzepatide induced significant and sustained weight loss (mean 19.7% at the highest dose) and markedly reduced the incidence of T2DM, compared with placebo (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval, 0.0 to 0.1). Notably, this protective effect persisted after a 17-week off-treatment period. 44
These findings underscore the dual benefits of OMMs in glycemic control and diabetes prevention, supporting their integration into obesity and diabetes management strategies to improve long-term metabolic health.
ASCVD
Obesity is a major risk factor for atherosclerosis, which contributes to metabolic dysregulation, systemic inflammation, and endothelial dysfunction. 70 Semaglutide 2.4 mg is the first OMM to demonstrate cardiovascular benefits. In the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial, semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% in individuals with overweight or obesity and established ASCVD, even in the absence of diabetes ( Table 4 ). 71 These effects were consistent regardless of glycemic status or sex. 72 , 73 Over 208 weeks, semaglutide 2.4 mg sustained a 10.2% weight loss, along with reductions in waist circumference and waist-to-height ratio, correlating with decreased visceral adiposity. 74 The cardiovascular benefits of GLP-1 receptor agonists are attributed to weight loss, improved insulin sensitivity, reduced inflammation, and direct effects on endothelial function and myocardial remodeling. 75 Accordingly, pharmacologic treatment should be prioritized to improve metabolic and cardiovascular outcomes in people with overweight or obesity and ASCVD.
Table 4
Cardiovascular outcome trials of obesity management medications in people with overweight or obesity
Obesity-related HFpEF
HFpEF is now the predominant form of heart failure (HF), largely due to increasing rates of obesity and aging. 76 Among its phenotypes, obesity-related HFpEF is characterized by systemic inflammation, vascular dysfunction, and metabolic derangement, making obesity a key therapeutic target. 77 Recent RCTs highlight the benefits of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists in this population ( Table 4 ). The Semaglutide Treatment Effect in People with Obesity and Heart Failure with Preserved Ejection Fraction (STEP-HFpEF) trial demonstrated that semaglutide 2.4 mg significantly reduced body weight and improved symptoms and functional capacity. 78 , 79 The SUMMIT trial found that tirzepatide not only reduced body weight but also lowered the risk of cardiovascular death or worsening HF and improved overall health status, suggesting potential advantages over GLP-1 receptor agonists alone. 80 , 81 These agents mitigate inflammation, 82 cardiac remodeling, 83 , 84 epicardial adipose tissue accumulation, 84 volume-pressure overload, 85 and cardiovascular or kidney injury. 85 The magnitude of clinical benefit correlates with the degree of weight loss. 86 Evidence from STEP-HFpEF and SUMMIT supports the use of these agents as therapeutic options for obesity-related HFpEF, although further studies are needed to assess long-term outcomes.
MASH
MASLD, formerly known as nonalcoholic fatty liver disease, is increasingly recognized as the hepatic manifestation of metabolic syndrome. 87 , 88 Incretin-based therapies, particularly GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have shown promise in modifying disease progression in MASH. The Liraglutide Efficacy and Action in Non-alcoholic Steatohepatitis (LEAN) trial demonstrated that liraglutide 1.8 mg achieved MASH resolution without worsening fibrosis in 39% of individuals with biopsy-proven MASH, compared with 9% with placebo. 89 A subsequent trial of semaglutide 0.4 mg reported MASH resolution without worsening fibrosis in 59% of participants with biopsy-confirmed MASH and F1–F3 fibrosis versus 17% with placebo. 90 The SYNERGY-NASH trial, which evaluated tirzepatide in individuals with biopsy-confirmed MASH and F2–F3 fibrosis, demonstrated MASH resolution rates of 44% to 62%, with significant improvement in fibrosis compared with placebo. 91 These findings support the therapeutic potential of incretin-based therapies in MASLD, particularly for individuals with overweight or obesity and MASH.
OSA
OSA is a common comorbidity among people with overweight or obesity, and weight reduction is an effective treatment strategy. 92 OMMs have been shown to reduce OSA severity and improve cardiometabolic outcomes. In an RCT, phentermine/topiramate ER combined with lifestyle intervention significantly reduced the apnea-hypopnea index (AHI), compared with placebo, with improvements in other OSA parameters and participant-reported outcomes as well. 93 In individuals with obesity without diabetes, liraglutide 3.0 mg also reduced AHI more than placebo over 32 weeks, accompanied by greater weight loss. 94 Tirzepatide was evaluated in the SURMOUNT-OSA trial, and both the 10 and 15 mg doses significantly reduced AHI compared with placebo, with concurrent weight loss and improved participant-reported outcomes. 95 Based on those findings, tirzepatide recently became the first medication approved by the U.S. FDA for the treatment of moderate-to-severe OSA in adults with obesity, alongside a reduced-calorie diet and increased physical activity. 96
Question 5. What additional factors should be considered when prescribing OMMs?
Fig. 1 summarizes key precautions for prescribing OMMs based on comorbid conditions.
Cardiovascular safety
Cardiovascular safety is a primary concern when selecting OMMs, particularly in individuals with established CVD or those at high cardiovascular risk. Certain medications are contraindicated or should be used with caution in these populations. For example, naltrexone ER/bupropion ER is contraindicated in individuals with uncontrolled hypertension due to its potential to increase blood pressure and heart rate. Even in those with controlled hypertension, regular monitoring is advised. 46 The cardiovascular safety of this agent in high-risk populations remains uncertain, as a cardiovascular outcomes trial was terminated prematurely, precluding definitive conclusions. 97 Phentermine/topiramate ER is generally avoided in individuals with coronary artery disease or a significant cardiovascular history due to its sympathomimetic effects. 46
Neuropsychiatric effects
Clinicians should remain vigilant about the potential neuropsychiatric effects of OMMs, especially in individuals with a history of mood disorders or current depressive symptoms. Naltrexone SR/bupropion SR, which contains the antidepressant bupropion, has shown mixed psychiatric outcomes in clinical trials; some studies have reported fewer depressive symptoms than placebo and no increase in depression or suicidal ideation. 16 , 34 - 36 Nonetheless, caution is warranted during initiation and dose escalation, particularly in adolescents and young adults. Concomitant use with serotonergic agents requires vigilance due to the potential risk of serotonin syndrome. 46 Phentermine/topiramate ER has demonstrated dose-dependent neuropsychiatric adverse effects, with higher doses associated with an increased risk of depression. 37 , 38 Topiramate and other anticonvulsants have also been linked to an elevated risk of suicide-related events, necessitating careful monitoring for mood disturbances, especially in individuals with a history of depression. 98
Concerns have also been raised regarding semaglutide and the potential risk of suicidal ideation. 99 Although regulatory reviews have not established a causal relationship between GLP-1 receptor agonists and suicidal or self-injurious thoughts, 100 some pharmacovigilance analyses suggest a higher rate of suicidal ideation, particularly among individuals concurrently using antidepressants or benzodiazepines. 101 In contrast, a real-world cohort study reported lower risks of both incident and recurrent suicidal ideation with semaglutide than with non–GLP-1 receptor agonist medications. 102 Further research is needed to clarify the neuropsychiatric safety profiles of semaglutide and other GLP-1 receptor agonists.
Practical and societal considerations
Pharmacologic treatment offers clinically significant benefits for people with overweight or obesity. However, its use should be guided by regulatory standards, evidence-based guidelines, and individualized clinical judgment. Shared decision-making is essential and should include discussions about expected therapeutic outcomes, potential adverse events, treatment duration, routes of administration, financial considerations, and individual preferences ( Fig. 2 ).
The recent emergence of highly effective medications with disease-modifying potential has substantially increased the clinical relevance of obesity pharmacotherapy. Nevertheless, several limitations in the current evidence base should be acknowledged to set realistic expectations. Most landmark RCTs are limited to relatively short durations (typically around 1 year), even though obesity is a lifelong, relapsing condition. In addition, the lack of head-to-head trials restricts the ability to make direct comparisons between pharmacologic agents. Furthermore, real-world evidence about OMMs, particularly in Korean or other Asian populations, remains limited, raising uncertainty regarding their long-term effectiveness, safety, and adherence in clinical practice.
From a societal perspective, ensuring appropriate and equitable use is paramount. One of the major barriers to pharmacologic treatment is the lack of reimbursement for any approved OMMs. This financial burden can limit access and adherence, particularly among vulnerable populations. 103 , 104 Policy support and cost-effectiveness evaluations are imperative. 105 Additionally, misuse of OMMs, including off-label or cosmetic use, unapproved drug combinations, and products obtained from unregulated sources, poses serious public health risks. Such practices undermine individual safety and erode public trust in medical care. Accordingly, clinicians must carefully assess the indications for pharmacologic treatment and, when necessary, refer individuals with severe or complex obesity to multidisciplinary or interprofessional teams with relevant expertise.
HEALTH FUNCTIONAL FOODS
In response to growing public interest, the 9th edition of the Clinical Practice Guidelines addresses health functional foods for obesity management for the first time. 6 Despite their widespread use, robust evidence supporting their long-term safety and efficacy remains limited because most available data are derived from short-term, small-scale studies. Products such as Garcinia cambogia , conjugated linoleic acid, green tea extract, probiotics, and carnitine have shown only modest and inconsistent effects on weight loss 106 - 111 and have been associated with adverse events, including gastrointestinal symptoms, hepatotoxicity, and cardiovascular complications 107 , 108 , 112 , 113 ( Table 5 ). 114 - 131 Although combination therapies involving health functional foods were once popular, the lack of strong supporting evidence and ongoing safety concerns have led to heightened caution. Moreover, unlike approved OMMs, these products are not subject to rigorous safety and efficacy regulatory standards or post-marketing surveillance. The absence of robust guidance and any monitoring system further complicates their appropriate use.
Table 5
Health functional foods for obesity management
Accordingly, this guideline does not recommend the use of health functional foods that lack sufficient evidence for weight management. Clinicians should counsel individuals with overweight or obesity on the limited benefits, potential risks, and regulatory uncertainties associated with these products. Well-designed, large-scale, and long-term trials are needed to rigorously evaluate their clinical usefulness and safety profiles.
LIMITATIONS
The current guidelines and this manuscript have several limitations. First, although recommendations were developed through a systematic literature review and rigorous adaptation process, several topics, such as older adults, mental health comorbidities, and health functional foods, lack high-quality evidence, resulting in recommendations that are largely consensus-based. Second, because the guideline emphasizes evidence relevant to Korean and East Asian populations, the generalizability of these recommendations to other racial and ethnic groups or healthcare systems could be limited. Third, the rapidly evolving landscape of obesity management, including the introduction of new pharmacotherapies, means that some recommendations could become outdated as new data emerge. Fourth, practical implementation barriers, such as limited insurance coverage, the accessibility of specific interventions, and variation in clinical practice, could affect real-world application and effectiveness.
CONCLUSION
The 9th edition of the Clinical Practice Guidelines for Obesity by the KSSO provide updated, evidence-based recommendations that reflect recent advances in scientific knowledge, novel therapeutic strategies, and emerging directions in obesity management. These guidelines adopt a risk-based, person-centered approach, redefining obesity as a chronic, relapsing disease and emphasizing the concept of clinical obesity beyond traditional BMI thresholds. Major updates include the integration of newly authorized pharmacologic treatments that achieve substantial weight loss and cardiometabolic improvements, the recognition of obesity-related health conditions, and the introduction of recommendations about health functional foods. The guidelines highlight the importance of assessing the treatment response early and making timely adjustments to optimize long-term outcomes. Treatment decisions should be guided by cardiometabolic risk and the overall health burden rather than by weight loss alone. In addition, the guidelines explicitly address practical and societal considerations, advocating for equitable access, shared decision-making, and the appropriate use of pharmacotherapies to maximize clinical benefit while minimizing risk. Altogether, the 9th edition underscores the expanding role of obesity care, marking a shift from symptomatic control toward disease modification. It also emphasizes the need for ongoing evidence appraisal and periodic updates to maintain alignment with best clinical practice in this rapidly evolving field.
SUPPLEMENTARY MATERIALS
Supplementary materials can be found online at https://doi.org/10.7570/jomes25042 .
ACKNOWLEDGMENTS
This work was supported by the Korean Society for the Study of Obesity.
Footnotes
CONFLICTS OF INTEREST
SuJin Song is an editorial board member of the journal. But she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
To assess potential conflicts of interest among all individuals involved in the development of these guidelines, a structured disclosure survey was conducted. Participants were asked whether they had received sponsorship or consulting fees related to obesity pharmacotherapy, held financial interests, such as stock options, in relevant institutions or pharmaceutical companies, or occupied official or unofficial positions within such companies. Based on the submitted disclosures, no actual or potential conflicts of interest were identified.
AUTHOR CONTRIBUTIONS
Study concept and design: JHB, JHH, and HK; acquisition of data: JHB, JHH, EJ, SYK, and SJS; analysis and interpretation of data: JHB, JHH, EJ, SYK, SJS, CYP, and HK; drafting of the manuscript: JHB, JHH, and HK; critical revision of the manuscript: JHB, JHH, EJ, SYK, SJS, CYP, and HK; statistical analysis: JHB, EJ, SYK, and SJS; obtained funding: HK; administrative, technical, or material support: HK; and study supervision: CYP and HK.
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