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by master_crab5 hours ago |
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upvoteby ramraj075 hours ago|
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They use a method called propensity score matching to try their best to match patients on both sides using a simple linear model with various features that try to ensure that only pairs of closely matched patient histories are compared.

Unfortunately this is rarely clean. Its also easy to make mistakes. Sometimes two arms are fundamentally incomparable. The quality and rigor of the comparison is often determined by a lot of extra checks and validations, and different journals demand different levels of rigor. I need to read it carefully to judge if this is good or not.

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upvoteby nxobject4 hours ago|
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It looks like both do standard individual covariate checks for post-match balance, with SMDs. I'm surprised they haven't assessed balance for at least pairwise interactions, too -- we should be balancing out joint risk factors too, no?

I haven't worked on these designs, but I remember the methodologist that taught me this in grad school giving us a lecture about this.

EDIT: the BMJ article (laudably) provides access to the analyis code, although I won't have time to review it:

github.com/nilskruger/Tirzepatide-and-the-Risk-of-Atherosclerotic-Cardiovascular-Events

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upvoteby yayamo5 hours ago|
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They already do acknowledge socioeconomic (and other confounding factors) in the analysis. The primary analysis they perform is a ‘Propensity Score Match’ which is a technique used specifically to address for confounders in observational studies, and they do report balanced cohorts. Still they write in their discussion “Although we adjus- ted for several available proxies of socioeconomic and lifestyle status, direct measures of income, insurance coverage, or out-of-pocket payment were not available in the TriNetX database. Residual confounding related to unmeasured socioeconomic factors, therefore, cannot be excluded“

Given the size of the dataset, the effect size, significance and sensitivity testing they did I think it’s very strong evidence for GLP1s causing this and it would be very very surprising to me to see the effect disappear even if they had perfect socioeconomic data.

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upvoteby joaopbnogueira5 hours ago|
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Or having a lower % of body fat (within healthy limits) is the factor improving a better immune response?
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upvoteby tptacek4 hours ago|
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Generally studies showing off-target effects with GLP1s are at least attempting to control for this.
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upvoteby mathgeek4 hours ago|
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I’d be interested to see the data for that claim, since I would imagine a strong correlation between glp use and lower body fat.
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upvoteby tptacek4 hours ago|
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I’m sure you can just look up the studies, but note that GLP1s are widely prescribed to people without weight issues —— weight loss itself was originally an off-target effect. I have friends who run marathons who are on semaglutide.
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upvoteby olalonde4 hours ago|
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This video by a medical doctor cites many studies showing that GLP-1 health benefits go beyond weight loss (see video description for link to papers): https://www.youtube.com/watch?v=yKPaVhpomks
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upvoteby Ecko1235 hours ago|
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[dead]
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upvoteby acheron5 hours ago|
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Wow, bet they never thought of that. If only the researchers had thought to ask HN first.
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upvoteby clickety_clack4 hours ago|
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Would you prefer that people accept claims uncritically? It’s a valid critique of the results.
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upvoteby wvenable4 hours ago|
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If the commenter read the study and found that they did not, in fact, account for that then it would be valid to point it out here.

Otherwise, it's just a waste of our time.

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upvoteby clickety_clack2 hours ago|
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By its fundamental design, an observational study cannot account for everything. That is the critique and it is a valid one.
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upvoteby wvenable1 hours ago|
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Most observational studies do in fact account for the first thing a random HN poster can come up with 5 seconds after reading the title. So there is very little value in such a comment.
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upvoteby ryanchants5 hours ago|
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They are also anti-inflammatory, so it could be related to less systemic inflammation.
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upvoteby maxall44 hours ago|
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The benefit is probably from the removal of fat, not a direct antibacterial/antiviral effect. Fat plays a complex immunoregulatory role in human physiology: it down-regulates some pathways, while up-regulating others (notoriously, the production of IL6 is carried out, in part, by adipocytes). The overall effect of fat on the immune system, however, is negative: it tends to increase the chances of rheumatological disorders, cancers, and many other diseases. Alternatively, the effect may be due to some sociological factor that their analysis failed to account for.

(I am not a medical doctor)

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upvoteby olalonde4 hours ago|
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Many of the health benefits, including cardiovascular and kidney health, have been shown to go beyond or be unrelated to changes in body weight.

https://www.youtube.com/watch?v=yKPaVhpomks

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upvoteby bitwize4 hours ago|
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Lower visceral fat as a percentage of body weight may bring benefits that are greater than proportional to total body mass lost.
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upvoteby tptacek3 hours ago|
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Nobody's denying this, but the interesting story about GLP-1s is that after you control for fat loss (for instance, by taking cohorts of patients that aren't losing weight) you still get evidence of these off-target effects.
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upvoteby DANmode3 hours ago|
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How much of “fat” also includes biofilmed infection stifling your electrical system and indeed signaling your immune system to not work as well?

(You can look this up regarding biofilms, I just did today.)

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