In an ongoing debate over a proposed new framework for the diagnosis of obesity set forth in 2025 by The Lancet Commission, the Endocrine Society has issued a guideline communication outlining its reasons for holding back its support of the proposal, questioning such concepts as the establishment of ‘clinical’ and ‘preclinical’ obesity, and other issues.

“We need simpler ways to identify obesity earlier that don’t involve rigid diagnostic thresholds,” said Amy Rothberg, MD, of the University of Michigan, Ann Arbor, Michigan, in a press statement on the Endocrine Society’s response, published this month in The Journal of Clinical Endocrinology & Metabolism.

Efforts should “focus on making sure people with obesity can access treatment based on how much it’s likely to improve their daily lives and how safe it is — not on proving a single, exact cause,” she said.

The Lancet Commission’s proposal came in response to widespread consensus that the standard measure of BMI alone falls short in accurately reflecting an individual’s obesity risk by failing to include other key conditions, including waistline circumference and waist-to-hip ratio, that are known to play key roles in an increased metabolic risk.

Ignoring such factors potentially overestimates the risk, for instance, in muscular individuals while underestimating risk in those with excess visceral or ectopic fat, experts have argued.

In its proposal, the Lancet Commission criteria includes those factors — and significantly more.

In terms of the proposal that obesity be classified as being preclinical or clinical, the framework requires evidence that organ dysfunction is caused by body fat for a diagnosis of clinical obesity, with preclinical obesity allocated to those without evidence of the organ dysfunction, among other criteria.

More than 75 medical organizations were listed as endorsing the report in its publication, including the American Association of Clinical Endocrinologists, the American Diabetes Association, and the American Heart Association.

However, some groups, in addition to the Endocrine Society, that have held back their endorsement and detailed the reasons, include the European Association for the Study of Obesity (EASO) and the Obesity Medicine Association.

Body Fat as a Cause of Organ Dysfunction Problematic

In its own response, the Endocrine Society underscores that key limitations of the framework include the criteria that proof of organ dysfunction caused by body fat is necessary for a diagnosis of clinical obesity, potentially causing delays or barriers in treatment.

“In routine practice, patients often have multiple interacting risk factors, making this determination difficult and potentially inconsistent across clinicians and settings,” Ranganath Muniyappa, MD, PhD, a senior clinician in the Clinical Endocrine Section of the Diabetes, Endocrinology, and Obesity Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Maryland, and first author of the Endocrine Society response, told Medscape Medical News.

Conditions such as atrial fibrillation, polycystic ovary syndrome, and hypertension, for instance, can arise from inflammatory, genetic, and various other influences, hence “demanding exclusive attribution provides little clinical value,” the authors noted in the Society’s response.

Furthermore, evidence that weight reduction improves outcomes regardless of the cause, likely through shared mechanisms, underscores that “treatment is justified without a singular causal narrative,” they underscored.

Causative Role of Diabetes in Obesity?

Another key point of contention is that the Commission omits type 2 diabetes from its list of obesity-induced organ dysfunctions, suggesting less of a role of causation over association, however, Muniyappa suggests that doing so “creates a disconnect between the framework and clinical reality.”

“It also raises broader concerns about causal attribution,” he said. “If a condition with such a strong relationship to adiposity is excluded, it becomes more difficult to understand how other conditions will be classified.”

“This may limit the framework’s clarity and reduce its usefulness in guiding both clinical care and policy decisions.”

Preclinical Obesity: ‘Conceptually Unstable’

Also problematic is the concern that a diagnosis of preclinical obesity could have the effect of delaying needed care by implying a pre-disease status.

But in real-world practice, “a label indicating no substantial dysfunction may be interpreted as low acuity, which could reduce access to therapies even in individuals with high risk,” Muniyappa explained.

“Overall, the framework may be resource-intensive and difficult to implement consistently across diverse clinical environments,” he added.

‘Harmonization’ With Other Obesity Staging Systems

To address those, and other concerns outlined in the paper, the Endocrine Society “advocates harmonization” with several obesity staging systems already in place that effectively characterize obesity for treatment and risk decisions, including the Edmonton Obesity Staging System, American Association of Clinical Endocrinology Adiposity-Based Chronic Disease and EASO models.

Such systems define obesity on scales of graded severity across the full spectrum of risk “rather than a sharp health-illness divide,” that is proposed in the Commission’s binary preclinical/clinical model, the Endocrine Society authors said.

The systems “align more closely with how clinicians make decisions, focusing on severity, complications, and overall risk rather than requiring strict causal attribution,” Muniyappa added.

“This makes them easier to apply in patients with complex comorbidities.”

Response: Critiques Reflect Key ‘Conceptual Confusions’

Commenting on the Endocrine Society’s assessment, Francesco Rubino, MD, who was the first author of the Lancet Commission’s framework and is chair of Metabolic and Bariatric Surgery in the School of Cardiovascular and Metabolic Medicine & Sciences, King’s College London, London, England, argued that the points raised reflect key misconceptions that the Commission is aiming to address.

“In a striking irony, the paper serves as a comprehensive catalogue of the very conceptual confusions that stem from the gap the Commission set out to resolve,” Rubino told Medscape Medical News.

While the Commission’s framework strives to provide “what obesity medicine has long lacked: A rigorous disease definition built on the same principles underpinning every other medical diagnosis, the critics evaluate this through the prism of staging tools and management frameworks — instruments that serve an entirely different function.”

That fundamental misreading drives “every objection [that critics] raise,” Rubino added.

Fundamentally, a clinical diagnosis exists for the sole purpose of determining whether active disease is present in an individual patient.

“It captures a clinical reality at a given moment. What follows — preventive or interventional — is a matter of management, not diagnosis,” Rubino explained.

The Society’s suggestion to “harmonize” the Commission’s diagnostic proposals with existing risk-based management tools is “equivalent to calling for harmonization between a pregnancy test and an antenatal care pathway,” he argued.

“One determines whether a condition exists, the other governs what to do about it.”

“They are not competing frameworks; they operate at entirely different levels of clinical logic.”

Rubino added that the suggestion that diabetes should indeed serve as a diagnostic criterion for clinical obesity is the Endocrine Society paper’s “most emblematic error.”

“Diseases are defined to delineate distinct entities — they do not incorporate other independent diseases into their own criteria,” he said. “This is precisely why obesity researchers already exclude diabetes from clinical trials. The Commission’s approach aligns with standard medical reasoning.”

Ultimately, Rubino asserted that “the answer the critics owe patients — and the field — is this: What purpose is served by obscuring the distinction between manifestations of obesity that call for fundamentally different care?”

The Lancet Commission reported receiving no outside funding. Rothberg reported having relationships with Boehringer Ingelheim, Fractyl, Eli Lilly, DLA Piper, Rewind Inc., American Board of Obesity Medicine: Board of Directors,Finance Committee, The Obesity Society: Finance Committee Chair, The Hormone Foundation: Trustee, University of Michigan: Clinical Excellence Society Treasurer/Secretary. Muniyappa had no disclosures to report. Rubino reported receiving research grants from Ethicon (Johnson & Johnson) and Medtronic; Speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, Amgen, and AstraZeneca; and consulting fees from Kailera and Astra Zeneca; he reported being a member of DSMB for GI Metabolic Solution Inc., and President of Metabolic Health Institute (non-profit).