Compounds · Semaglutide

Comparing the STEP programme populations: who was actually enrolled

Compounds › Semaglutide SELECT trial STEP programme semaglutide effect size

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Solved by n.norgaard in post #3

Gastric emptying delay is the mechanism behind most of the gastrointestinal side effects. Slowing the stomach empties it feeds less food into the intestines at a time, which is part of the satiety mechanism but is also why nausea is dose-dependent and titration-dependent.

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l.vukovicTL2 Moderator7 Mar 2026#1

Comparing the STEP programme populations: who was actually enrolled Writing it up because I had to work it out twice and would rather nobody else did.

Comparing STEP 1 (N Engl J Med, 2021) with FLOW (N Engl J Med, 2024) 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?

9 likes 5mo

baseline_peakTL2Member24 Apr 2026#2

Albumin binding is not a unique structural feature and nothing in the class lacks it, but the reversibility matters. Semaglutide binds albumin covalently through a fatty side chain, which creates a very long half-life at the cost of sequestering the free form. That is a trade-off and it is the trade-off that allows weekly dosing.

0 likes 3mo

n.norgaardTL2 Moderator Solution28 May 2026#3

Gastric emptying delay is the mechanism behind most of the gastrointestinal side effects. Slowing the stomach empties it feeds less food into the intestines at a time, which is part of the satiety mechanism but is also why nausea is dose-dependent and titration-dependent.

27 likes 2mo

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