Who Was Actually in the Trials

Every result on this register comes with an unstated question: does it apply to you? A systematic review answered it directly, examining the baseline characteristics of 246 randomized trials covering 139,566 participants across twelve obesity medications and three decades.^[1] The people studied are not the people affected, and the mismatch has a consistent shape.

Who was over-recruited, and who was missing

The people with the most severe obesity are the least represented in the evidence for treating it.

That last row deserves the most attention, because it is backwards. People with class 3 obesity have the most to gain from an effective treatment, are the most likely to be prescribed one, and are the group a clinician is most confident about recommending it to. They are also the group the trials studied least.

What this does and does not mean

Uncertainty is not the same as bad news, and it is not nothing either. A confidence interval reported for a trial population applies to that population. Extending it to a group who made up a small fraction of participants is an act of judgment, usually a reasonable one, and always a step beyond what was measured.

There is one relevant piece of reassurance. Where a rare genetic subtype of obesity has been examined inside a trial, response was comparable to everyone else — genetics caused it and the drug still worked. That is a different question from demographic representation, and it points the encouraging way.

There is a second example of what happens when someone does go looking, and it points the same encouraging way. Adults aged 40 or under are explicitly underrepresented in type 2 diabetes trials — a post hoc analysis of the SUSTAIN and PIONEER programs went back and examined them separately, and found semaglutide reducing HbA1c and body weight across every age subgroup, particularly in young adults, with comparable rates of serious adverse events.^[2]

That is the useful shape of a response to this problem: not assuming an underrepresented group responds the same, and not assuming they do not, but going back to the data and checking. Both times anyone has checked here, the answer has been reassuring.

Where this shows up in specific trials

Once you know the pattern, it appears in almost every trial this register covers. These are not criticisms of individual studies; they are the same systematic skew, one paper at a time.

• 82.4% women in the genome-wide study of who responds, which was also restricted to European ancestry — the genetics are real, and small.
• 92% women, mean age 64 in the bone density study, which shapes everything it found — bone density and fracture risk.
• 75% men, median age 68 in the peripheral artery disease trial — the opposite skew, for a condition that skews that way — how far you can walk.
• 85% White in the retatrutide body composition substudy.
• Chinese BMI thresholds and a mean age of 33 in a phase 2b trial whose results do not transfer straightforwardly — the drugs that are not here yet.

The BMI question has a second dimension the review does not address. Obesity is defined at a BMI of 25 rather than 30 in many Asian populations because risk rises at lower body mass — so a trial recruiting at class 1 and class 2 by Western thresholds is recruiting a different metabolic population than the same numbers would describe elsewhere. That is in the BMI threshold is not universal.

What to do with it

• Check the baseline table, not just the result. Every trial publishes who was in it, and it takes ten seconds to see whether that includes people like you.
• Treat effect sizes as estimates from a described population, which is what they are, rather than as universal constants.
• Do not read under-representation as evidence of worse response. It is evidence of not knowing.
• Expect this to improve slowly. The review’s own recommendation is that future trials recruit the groups they have been missing, which is the right conclusion and a slow one.

For what these numbers look like when applied outside a trial altogether, see what these drugs do outside a trial and who responds in the real world.