FLOW got published and nobody in here is talking about eGFR slope
FLOW (Perkovic et al., N Engl J Med, 2024) reported a hazard ratio of 0.76 for the composite kidney endpoint in people with type 2 diabetes and chronic kidney disease. The front page spent a week on a weight-loss thread.
The part I want to argue about is the eGFR slope. A slower rate of decline is not a headline number and it is arguably the most consequential thing in the paper, because slope is what determines whether somebody reaches dialysis in their lifetime.
This is a different category of finding from a percentage of body weight, and this community treats every readout as if it were the same category.
best — the order this archive was captured in
Agreed, and the reason slope gets ignored is that it does not fit the format everybody uses to discuss these drugs. A hazard ratio is a single quotable number. A slope is a rate, and a rate needs a timeframe to mean anything.
Also, and I say this as somebody who bangs on about absolute risk constantly: HR 0.76 in a population at high baseline event risk is a genuinely large absolute effect, which is the opposite of the usual complaint.
yes — this is one of the trials where the relative number understates rather than overstates, because the baseline risk is so high.
which makes it one of the few readouts where I do not have to demand the number needed to treat, because it is small enough to be obviously worth it.
and the confidence interval is narrow, which for a composite endpoint in a CKD population is not guaranteed.
watch where the curves separate too. early separation on a kidney endpoint is more surprising than early separation on weight.
that is the figure i keep going back to. it is earlier than i would have predicted.
same argument applies to the hepatic side and survodutide. the MASH biopsy endpoints are a different category of evidence to a weight percentage and they get a fraction of the discussion.
my creatinine ticked up during rapid loss and settled. hydration confounds everything at the individual level, which is exactly why trial-level slope data matters and my n=1 does not.
Good post, correct flair, publication rather than press release. Stickying for the week. Reminder that Press Release flair is mandatory until a paper exists — we had three threads last quarter arguing about numbers that had never been published.
worth checking whether the slope analysis was pre-specified. edit: it was, which is more than I expected.
this is a diabetes and CKD trial being used to argue about a weight-loss drug. different population, different question.
correct, and the post is arguing that we should stop collapsing them into one conversation. you have agreed with me in the form of a disagreement.
- 1Agreed, and the reason slope gets ignored is that it does not fit the format…6 comments in this branch · started by u/hazard_ratio_hal