What the GIP component of tirzepatide is thought to contribute, and how confident we can be

What the GIP component of tirzepatide is thought to contribute, and how confident we can be I have a specific reason for asking rather than idle curiosity, and the context is below.

Comparing STEP 1 (N Engl J Med, 2021) with SCALE (N Engl J Med, 2015) and finding the comparison harder than it looks.

Different populations, different durations, different endpoints defined slightly differently, and in one case a different estimand. People compare the headline percentages anyway, including me until recently.

Is there a defensible way to put these side by side, or is the honest answer that there is not and we should stop?

Picking up post #2: that is the part I would want checked first.

SURMOUNT-1 reported weight reduction of a magnitude that was the largest for a pharmacological intervention at that time of publication. It also reported a clear dose response across three doses. The categorical thresholds (people reaching 10%, 15%, 20% loss) got the most attention but read less informatively than the mean weight change.

The GIP component: GIP receptor agonism is thought to amplify the GLP-1 effect on satiety and energy expenditure, but how much of tirzepatide's effect is that and how much is simply achieving higher receptor occupancy remains genuinely open. The mechanistic literature is active.

Worth separating two things that post #16 runs together.

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.