[brianleb]

GLP-1 => weight loss => decreased obesity, improved cholesterol, improved blood pressure, improved glucose control, etc. etc. => better survival rates (all causes)

There is no presumed clinically relevant mechanism for GLP-1s to be protective specifically against COVID death. It is simply protective against all death, of which COVID is a type. Healthier people are less likely to die, statistically. The same benefit can be (and is being) said about GLP-1s and heart attacks, heart failure, stroke, kidney failure, etc.

[wswope]

Rather arrogant of you to spew forth unfounded conjecture without even bothering to skim the high-level details of a six paragraph article.

> the protective effect occurred immediately — before participants had lost significant amounts of weight.

> the participants taking the drug were not healthier than the others, said Dr. Harlan Krumholz, a cardiologist at Yale and the editor in chief of the journal.

[brianleb]

I understand how you came to your conclusion, however what you are quoting is journalism (and it is factually incorrect). I read the actual peer reviewed article.

The patients in the COVID group, _when they got COVID_ had already begun losing significant amounts of weight. The NYT article is 100% incorrect on this matter. See:

>>The change in weight between randomization and reported COVID-19 in patients who died of COVID-19 according to treatment was −6.4 kg in the semaglutide group vs −0.9 kg in the placebo (P < 0.001) group and −8.4 kg vs −1.25 kg (P < 0.001), respectively, in patients who did not die.

They go on to say that there is a correlation between obesity and adverse COVID outcomes:

>>There was an associated increased risk of respiratory decompensation and mortality in patients with COVID-19 and obesity16,17 and plausible biologic hypotheses associating obesity with adverse COVID outcomes, including impaired respiratory status, lower cardiometabolic reserve, or immune hyperreactivity or dysregulation.18

And they double down on the fact that the patients absolutely had weight loss at time of COVID.

>>Accordingly, it is plausible that the decreased risk of infectious deaths is caused by weight loss, which was 5 kg greater in patients assigned to semaglutide compared to placebo by 1 year, the average time to COVID-19 diagnosis after randomization.

I will leave you with the note that nowhere in the journal article do they make any claims whatsoever about semaglutide's effect on COVID outcomes. They exclusively discuss outcomes as related to metabolic health. Semaglutide is a means to an end. The means is weight loss. The end is better health.

[wswope]

I read the JACC article too, and thought the NYT claims were decently supported:

> The second unexpected observation was the lower rate of non-CV death with semaglutide vs placebo, particularly infectious deaths, including in patients with reported cases of COVID-19. The mechanism by which semaglutide is associated with lower CV or non-CV mortality is unknown. Weight loss improves traditional cardiometabolic and kidney risk factors,3 such as hypertension, dyslipidemia, renal function,26 and dysglycemia. However, the blood pressure and lipid reductions in SELECT with semaglutide were relatively small compared with those in dedicated risk factor–lowering trials, and the observed reduction in major adverse cardiovascular events is more than would be expected based on those changes.

You could absolutely be right that body weight is a lagging indicator, and these patients are getting a bigger improvement in systemic inflammation/their hematologic profile than weight loss alone would suggest… but running immediately to that conclusion is major hubris in my book. I don’t think it’s remotely implausible that there are one or more yet-unknown metabolic pathways tweaked by GPL1 agonists that could explain the effect.