Selecting between pharmacotherapy and bariatric surgery in East Asia

Abstract

The emergence of highly effective incretin-based therapies has transformed the treatment landscape for obesity, raising an increasingly important clinical question: which patients should receive pharmacotherapy, and which should undergo metabolic and bariatric surgery (MBS)? Although therapeutic options have expanded substantially, direct comparisons within comparable patient populations remain limited. Leslie et al.¹ addressed this question by comparing semaglutide, tirzepatide, and sleeve gastrectomy in a large real-world cohort of adults with type 2 diabetes and a body mass index (BMI) of at least 35 kg/m². At 1 year, the adjusted probabilities of achieving the primary composite outcome of ≥20% weight loss and an HbA1c level below 5.7% were 3.0%, 13.2%, and 24.0% with semaglutide, tirzepatide, and sleeve gastrectomy, respectively¹. This study provides an important foundation for reconsidering how obesity treatments should be compared and selected in contemporary clinical practice.

These findings should not be interpreted as establishing a universal hierarchy of obesity treatments. Treatment assignment was not randomized, and patients who underwent surgery were younger, had a higher BMI, and had a lower baseline HbA1c level than those receiving pharmacotherapy. Moreover, when the weight-loss threshold was lowered from 20% to 10%, the relative ranking of tirzepatide and surgery for the composite outcome was reversed. These observations illustrate that the relative effectiveness of obesity treatments depends both on patient characteristics and the outcomes used to define treatment success. This perspective is particularly relevant to East Asia, where differences in obesity phenotype and clinical priorities may influence how pharmacotherapy and MBS should be compared and selected.

The relationship between BMI and obesity-related disease differs substantially between East Asian and European-ancestry populations. At the same BMI, East Asians generally exhibit greater visceral and ectopic fat accumulation than individuals of European ancestry². Consequently, applying the same BMI threshold may identify patient populations with distinct patterns of body-fat distribution, metabolic risk, and obesity-related complications. Accordingly, patients who meet the same BMI criterion may represent biologically distinct obesity phenotypes, underscoring the need for caution when extrapolating comparative treatment data across populations.

Direct comparisons of fat distribution and body composition between East Asian and European-ancestry populations are limited among individuals with severe obesity, such as those included in the study by Leslie et al.¹ (mean BMI, 43.0–47.6 kg/m²). Nevertheless, potential differences in obesity phenotype should be considered when extrapolating. Even when similar weight loss is achieved, its clinical significance may differ depending on whether the predominant abnormality is subcutaneous fat accumulation or visceral and ectopic fat accumulation. These considerations underscore that obesity treatments should be evaluated not only by the magnitude of weight loss but also by changes in body composition and obesity-related complications.

The study by Leslie et al.¹ further highlights that the relative effectiveness of obesity treatments depends on the outcome being evaluated. Sleeve gastrectomy produced the greatest weight loss, whereas tirzepatide achieved the highest probability of achieving HbA1c <5.7%. These findings underscore the importance of evaluating obesity treatments across multiple clinically relevant outcomes, including cardiovascular and kidney disease, heart failure, metabolic dysfunction-associated steatohepatitis (MASH), obstructive sleep apnea, and body composition, rather than focusing solely on weight loss. However, comparable evidence from East Asia remains limited across many of these outcomes, particularly studies directly comparing pharmacotherapy with MBS. Table 1 summarizes the current evidence and highlights priorities for future comparative research in East Asia.

Direct comparisons are beginning to emerge in East Asia. In a prospective, nonrandomized, single-center study from China, patients with a mean BMI of approximately 32 kg/m² chose sleeve gastrectomy or semaglutide through shared decision-making. At 12 months, total weight loss was 28.6% with surgery and 11.3% with semaglutide³. Although this study provides one of the first direct comparisons in an East Asian population, its implications for treatment selection remain limited. The primary outcomes focused on changes in body weight and BMI, without evaluating remission of obesity-related complications. Moreover, semaglutide was administered at a maximum maintenance dose of 1.5 mg once weekly for a planned treatment duration of only 24 weeks, after which most patients discontinued therapy. Consequently, the study provides limited insight into the comparative effectiveness of surgery versus long-term semaglutide treatment at the currently approved dose for obesity. Future comparative studies using contemporary treatment regimens should evaluate not only sustained weight loss but also obesity-related complications, body composition, and long-term treatment durability to better inform individualized treatment selection.

Treatment effects may also differ with respect to body composition. In a real-world cohort, both glucagon-like peptide-1 (GLP-1) receptor agonists and bariatric surgery reduced fat mass and fat-free mass, but the relative changes differed between treatments. At 12 months, the percentage reduction in fat-free mass from baseline was smaller in the GLP-1 receptor agonist group than in the surgery group; however, fat-free mass loss accounted for a greater proportion of total weight loss in the GLP-1 receptor agonist group. Surgery was associated with greater fat-mass loss and a larger increase in the fat-free mass-to-fat mass ratio⁵. However, causal inference is limited by the retrospective study design, baseline differences between treatment groups, use of bioelectrical impedance analysis, and uncertainty regarding drug dose and treatment persistence. Nevertheless, these findings suggest that treatments achieving similar weight loss may produce clinically meaningful differences in body composition, underscoring the need for comparative studies in East Asian populations that evaluate body composition alongside obesity-related complications rather than relying solely on the magnitude of weight loss.

Treatment effects may also vary across populations according to the outcome evaluated. Although glycemic control and weight reduction with GLP-1 receptor agonists have generally been comparable between Asian and White participants, an updated meta-analysis demonstrated a greater relative reduction in major adverse cardiovascular events among Asian participants than among White participants (HR 0.73 vs. 0.86)⁶. These observations indicate that treatment effects may differ across populations in an outcome-specific manner. However, because most studies aggregated diverse Asian populations, they do not permit conclusions specific to East Asia, highlighting the need for region-specific comparative evidence. Taken together, these observations reinforce the importance of evaluating obesity treatments according to both population characteristics and clinically relevant outcomes, rather than assuming that findings from one population can be directly generalized to another.

If obesity phenotypes differ across populations and treatment effects vary according to the outcomes evaluated, weight loss alone cannot determine the optimal treatment for an individual patient. Instead, treatment selection should begin by identifying each patient's obesity-related complications and therapeutic priorities, followed by balancing the expected benefits and risks of pharmacotherapy and MBS for those specific outcomes. This represents a shift from maximizing weight loss to matching treatment strategies with the outcomes that matter most to each individual patient.

Several clinical prediction models have been developed to predict diabetes remission or weight loss after MBS, whereas comparable pretreatment predictors for incretin-based therapies remain limited. More importantly, existing prediction tools are largely treatment- and outcome-specific, designed to estimate the likelihood of response to a given intervention rather than identifying the optimal intervention for an individual patient. Their performance and generalizability in East Asian populations also remain uncertain. Future prediction models will likely integrate clinical characteristics, fat distribution, body composition, biomarkers, genetic information, and other multi-omics data to support individualized treatment selection as well as outcome prediction. Ultimately, these models should guide individualized treatment selection according to each patient's disease phenotype and therapeutic priorities.

Treatment selection should not be viewed as a one-time choice between two alternatives. In clinical practice, patients may transition from pharmacotherapy to MBS, require adjunctive pharmacotherapy for residual obesity-related complications or weight regain after surgery, or undergo planned combination therapy. Leslie et al.¹ excluded patients who crossed over between treatments and therefore could not evaluate treatment transitions, sequencing, or combination strategies. Ultimately, personalized obesity care will require determining not only the most appropriate treatment but also the optimal timing, sequence, and combination of therapies for each patient.

The study by Leslie et al.¹ provides an important real-world comparison of contemporary obesity pharmacotherapy and MBS. Future studies from East Asia should build on this framework by directly comparing treatments in populations with similar baseline characteristics, follow-up durations, and clinically relevant outcomes, while accounting for differences from European-ancestry populations in fat distribution, body composition, age, BMI range, and patterns of obesity-related complications. Multidisciplinary centers providing integrated care spanning lifestyle intervention, pharmacotherapy, and surgery will be essential clinical and research platforms for developing individualized, longitudinal treatment strategies. Ultimately, obesity care should move beyond asking which treatment is best to asking which treatment is best for a given patient, at a given stage of disease, and for the clinical outcomes that matter most.

D.Y. received clinically commissioned/joint research grants from Nippon Boehringer Ingelheim, Tanabe Pharma, Kowa, and ARKRAY. D.Y. also received consulting or speaker fees from Sumitomo Pharma, Tanabe Pharma, Kowa, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, and Eli Lilly Japan K.K. The other authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.