The BMI Threshold Is Not Universal

Obesity is defined at a BMI of 30 in the United States. In many Asian populations it is defined at 25, consistent with World Health Organization guidance, because cardiometabolic risk rises at lower body mass.^[1] Two phase 3 trials have now been run at those lower thresholds — and the gap between where risk starts and where eligibility starts is a real problem for real people.

Why the number differs

BMI is a ratio of weight to height, and it says nothing about what the weight is made of or where it sits. At the same BMI, people of South and East Asian descent tend on average to carry more visceral fat — the metabolically active kind around the organs — and less muscle than people of European descent.

The consequence is that type 2 diabetes, high blood pressure and cardiovascular disease appear at lower BMIs. A threshold calibrated on one population, applied to another, sets the line in the wrong place.

What the two trials found

In STEP 11, 78% reached a 10% reduction and 53% reached 15%, with waist circumference down 11.9 cm against 3.0 cm on placebo. Serious adverse events occurred in 13% on semaglutide against 8% on placebo. In OASIS 2, gastrointestinal effects hit 63.4% against 34.8% — and only 4.5% stopped because of them, which is a low figure for this class.

The comparison we are not going to make

What can be said without inventing anything: each trial beat its own placebo arm decisively, which is what a placebo-controlled trial is for. Whether response differs by ancestry is a question that requires a trial designed to ask it.

One detail complicates the threshold story and belongs here for honesty. STEP 11 admitted people from a BMI of 25 upward — and the average BMI of those actually enrolled was 31.3. The lower threshold widened who could enroll; it did not produce a trial conducted in people at BMI 25. What the drug does at the bottom of that range is less well characterized than the entry criterion suggests.

What follows from it

• A BMI number is not self-interpreting. The same figure carries different risk depending on ancestry, body composition and fat distribution.
• Eligibility rules and clinical risk are different things. Failing a BMI threshold is a statement about a rule, not about your metabolism.
• Waist circumference is the cheap correction. It reflects visceral fat directly, and it is the adiposity measure that tracked cardiovascular benefit in the largest analysis available — losing weight predicted more heart attacks.
• Oral dosing at 50 mg is a different drug from oral dosing at 7 or 14 mg, which is worth remembering when comparing oral results — see comparing trials that never met.

For the broader question of who actually needs treatment and why BMI is a poor instrument for deciding, see beyond BMI.