Editor's note: Michael Mindrum, MD, FRCPC, is an internist and obesity medicine physician at Dalhousie University in Nova Scotia. I asked him to write about metabolically healthy obesity, a label that can decide who gets treated. The day he sent me this essay, Nature Medicine published a review from Samuel Klein's group on what separates metabolically healthy from unhealthy obesity; his essay asks what that means in the exam room. His patient is Canadian; American clinicians will recognize every step of her story. (Michael Albert, MD)

Sara felt she had obesity for most of her life, an identity assembled from social cues, her mother's food policing, diets that began at 13, and cutting remarks from partners and even strangers. Physicians had recommended weight loss for ailments she was certain had nothing to do with her body fat, and she left those visits feeling unheard, dismissed and judged.

Around 50, as perimenopause arrived, Sara noticed a change. Her body had become more apple shaped. Her blood pressure climbed high enough that she was started on a pill. Her doctor told her she had prediabetes, an ultrasound showed a fatty liver, and a sleep study for her snoring found mild apnea. Her labs now met the criteria for the metabolic syndrome.¹² Both of her parents had type 2 diabetes, and she began to worry.

So she went to work. She lost 30 pounds (14 kg) on a lower-carbohydrate, higher-protein diet and long daily walks, and held it for most of a year. Her blood pressure fell so far that her doctor stopped the pill, her blood sugar returned to normal, and her partner said she stopped snoring. Then came a new job, less movement, more hunger and food noise, and the weight insidiously returned, the way it had more times than she could count. She had now regained half the weight she had lost.

Now 52, she worked up the courage to ask her family doctor about the new obesity drugs. Her BMI was 34. Her blood pressure was 128/84, her fasting glucose 99 mg/dL (5.5 mmol/L) and her triglycerides 142 mg/dL (1.6 mmol/L). The prior authorization was denied; she was, as her doctor put it, "too healthy on paper." Sara had what some in the literature call metabolically healthy obesity. After a lifetime of being told to lose weight, she was now too healthy to be treated.

This all raises the question: what does metabolically healthy mean? When do the benefits of treatment outweigh the risks? And if we treat, how far should we go before weight management becomes cosmetic, or medical authority lent to anti-fat bias?

Obesity harms health along two routes. One is mechanical: the weight of fat pressing on the joints, diaphragm, airways and stomach. The other is metabolic, governed less by how much fat a person carries than by where it sits and how it behaves.¹³

Fat is not inert. It is an endocrine and immune organ, a safe haven for storing and releasing energy. Healthy fat cells multiply rather than swell, stay small and uninflamed, and release fatty acids at just the right pace for our metabolic demand. Healthy fat tends to settle on the hips and thighs in the characteristic pear-shaped figure, whereas the apple shape is fat deposited centrally, with a tendency to overflow into and around the organs. Waist circumference, waist-to-height ratio and the body roundness index all track that central fat, and so add information about metabolic risk that BMI alone misses.^14,15

Harold Bays named the failure of safe storage adiposopathy, or "sick fat."¹⁶ Roy Taylor added that each of us has a personal fat threshold, the point at which fat storage under the skin exceeds its capacity, its adipocytes swell and inflame, and fat spills into the liver, the pancreas and the heart.^17,18 The process can whisper along for years before hypertension, fatty liver, diabetes or coronary disease declares itself. Metabolically healthy obesity implies the absence of all of this, and given the gravity and prevalence of metabolic disease, that is a bold claim.

In 2014 Juan Pablo Rey-López and colleagues reviewed 27 population studies and counted 30 definitions of metabolically healthy obesity. Among adults with obesity, its prevalence ran from 6% in an American sample, when insulin resistance (HOMA-IR) and metabolic syndrome criteria were both applied, to 75% in a British one, when only blood pressure, total cholesterol and type 2 diabetes counted: a 12-fold spread that owes as much to semantics and sampling as to biology.¹ Tighten the definition and the label all but disappears. In US survey data, 12.2% of adults met every criterion for what the authors called optimal metabolic health, including a normal waist and a blood pressure below 120/80; among adults with obesity, 0.5% did, a figure that says as much about the waist criterion as about their metabolism.¹⁹

Every definition rests on dichotomies such as these: blood pressure above or below 130/85, glucose above or below 100 mg/dL (5.6 mmol/L), triglycerides above or below 150 mg/dL (1.7 mmol/L).¹² A fasting glucose is healthy at 99 mg/dL and disordered at 100. Few definitions measure liver fat or inflammation, and all of them rest on a snapshot rather than a trend.

The strictest definition, set out in a new Nature Medicine review from Samuel Klein's group, requires normal insulin sensitivity together with a normal fasting glucose, oral glucose tolerance, lipid profile and liver fat.³ By that standard, metabolically healthy obesity is real, but only a small subset of people with obesity meet it.² Liver fat is the piece most definitions miss: in a Greek cohort followed for 10 years, 29% to 39% of people labeled metabolically healthy by metabolic syndrome criteria already had fatty liver on validated scores, and fatty liver marked those who would later lose the label.²⁰ Sara's numbers on paper (blood pressure, fasting glucose, triglycerides) don't measure her liver, the organ her ultrasound had already flagged.

As I look at Sara's clinical situation, I see a movie rather than a snapshot, and I consider what it predicts about her future. At her lightest, her energy, her sleep and her metabolic markers (glucose, triglycerides, C-reactive protein) all sat in healthy territory. At her heaviest, she met the criteria for metabolic syndrome, a hallmark of insulin resistance and raised cardiovascular risk. Now she sits between those two states, and she can tell which way she is traveling. So can I.

She is not unusual: metabolically healthy obesity is often a passing state. Between a third and a half of people labeled metabolically healthy become unhealthy within 4 to 20 years,^2,4 and in the Nurses' Health Study, 84% of women with metabolically healthy obesity had lost the label within 20 years.²¹ Keeping the label does not erase the risk. Women who kept it throughout follow-up still had a higher risk of cardiovascular disease than metabolically healthy women of normal weight (hazard ratio 1.57),²¹ and a meta-analysis of 23 prospective cohorts found the same excess even when no metabolic risk factor was present.²²

Payers fund what the highest grade of evidence proves (Level 1a, Grade A: large randomized trials). Some of that evidence includes people like Sara. STEP 1 enrolled adults with a BMI of 30 or more whether or not they had a complication,⁵ and in SURMOUNT-1, three years of tirzepatide in people with obesity and prediabetes cut new cases of type 2 diabetes from 13.3% to 1.3%.⁶ But the trials that test benefit to the heart, airway, liver and joints enrolled people who already carried the complication: established cardiovascular disease, moderate to severe sleep apnea, fatty liver with scarring, heart failure, and painful knee osteoarthritis.^7–11 In Canada, the national drug agency now recommends public coverage of semaglutide only for adults who have already had a heart attack, a stroke or symptomatic peripheral arterial disease.²³

The guidelines go further, but their recommendations remain honest to the level of evidence that supports them. In the field of obesity, the case that treating early prevents heart attacks, strokes and early death rests not on large randomized trials but on lower-grade evidence: population studies, genetic studies pointing to cause rather than coincidence,²⁵ and mechanisms we can see in the tissue. Obesity Canada recommends medication for adults like Sara, with a BMI of 30 or more, on its highest grade of evidence (Level 1a, Grade A), and on expert consensus urges considering it early in the natural history of obesity;²⁶ the European Association for the Study of Obesity, the American Diabetes Association, The Obesity Society and the Obesity Medicine Association point the same way.^27–29 The trial that would prove prevention, 20 years of drug against placebo in people who are still "well," is unlikely ever to be funded. The closest thing under way, SURMOUNT-MMO, an outcome trial of tirzepatide in more than 15,000 adults with primary completion expected in late 2027, still requires established cardiovascular disease or, for prevention, an older age and several risk factors. At 52, Sara would not have qualified.²⁴

So prevention is recommended but often not reimbursed, by public or private insurers, and a denial can imply that Sara does not deserve treatment. Labels such as "metabolically healthy" or "preclinical" obesity can send patients, physicians and payers the same message: treatment is not appropriate here. What fills the gap is clinical judgment and expertise. We know the published evidence, but we also listen to patients' stories and pick up the patterns in them. We develop bedside expertise and an evidence-informed way of personalizing care, and we understand that a lack of evidence of benefit is not proof that treatment does not help. Metabolic health is a spectrum, and so is the benefit of treating it.

For the sake of argument, let's accept that Sara is metabolically healthy. Obesity Canada defines obesity as abnormal or excess body fat that impairs health.³² By that definition a high BMI without impairment is an attribute of the body, like brown or blue eyes. On today's numbers alone, the Lancet commission's framework would call Sara's state preclinical obesity: the risk is raised, but organs still work normally.³³ Even that is not settled. In the commission's framework, metabolic health and organ health are different things (normal labs can sit beside obesity-related breathlessness or knee pain), and Sara's labs say nothing about the liver her ultrasound flagged or the apnea her sleep study found. The commission also allows intervention to reduce risk in preclinical obesity, matched to each person's level of risk.³³ The American Association of Clinical Endocrinology calls preclinical obesity stage 1 of the disease and treats it to prevent onset.³⁴

Is there a problem with calling someone like Sara "preclinical"? I think there is, and one example shows why: would we call a blood pressure of 150/90 "preclinical" until it caused a stroke? The frameworks are careful; the way their labels get used, on a coverage form, is not. I raise it to show a real challenge: medicine needs categories, words and semantics to communicate and to study, and those words carry verdicts. In the end, words matter.

Whether to treat is half the question. The other half is how far. Think of her personal fat threshold as a waterline. Perhaps we treat to just below the waterline, where Sara's glucose, triglycerides and liver come back to where she no longer meets the definition of metabolic disease, and go no further. Or do we treat to widen the buffer between her health and that waterline, keeping her safely below her personal fat threshold? Klein's group has measured both sides of that choice. A 5% weight loss improved insulin sensitivity in liver, muscle and fat, and further loss brought further gains,³⁵ but in women who lost about 20% of their weight, the improvement depended on how insulin resistant they were at the start and leveled off once insulin action was normal: a physiological version of the waterline.³⁶ The waterline is a useful metaphor, not a validated target weight, and a plateau in insulin sensitivity does not mean that further weight loss offers no other benefit, for sleep, joints or function. Somewhere past the waterline, treatment may stop being about metabolic health and start being about the size or appearance of the body, measured against a social standard that may itself be unhealthy.

If Sara wants to weigh less because she will move better, sleep better or feel more herself, that is a gain we can measure before and after.³⁷ If the goal is a number that would finally quiet her mother's voice, appearance rather than health, that goal deserves exploring before a prescription is written, because past a point the risks (nausea, gallstones, pancreatitis, loss of lean mass) can begin to outstrip the benefits.⁵ Eating less on these drugs can also look like success while masking underlying psychological problems such as an eating disorder. Atypical anorexia nervosa, restriction with all the medical danger of anorexia in a body that is not underweight,³⁸ is easy to miss in someone whose diets began at 13 and who is now praised for losing weight.

With Sara, I go in with my eyes open as I would with any patient. I listen to her weight story, to the bias and stigma she met in her childhood home and in her relationships. I listen to her goals and values. Sara wants her best health: not just to avoid type 2 diabetes, but to wake rested, to move better and to feel better. She wants to be there for her grandchildren. She tasted that feeling of being "herself" at her lightest weight two years ago, the time she felt most optimistic about her health and her future. And I weigh all of the evidence on her metabolic health and risk, now and in the years ahead.

Sara has been trying for a lifetime to lose weight and keep it off, and it would be a disservice to discount that or to tell her there is nothing wrong. Together we can aim treatment where there is health to be won, decide where it should hold, and keep a cautious eye on the point where we have moved from gaining health into something else. Her insurer read the form and said no. But clinical medicine is not a cookbook. It is a partnership, and there is more to it than any checklist can hold: the evidence, the story, and the judgment to know what we are treating, and how far to go.

Sara is a composite drawn from patients in my practice; names and identifying details have been changed.