Breaking news: Wegovy lowered Covid-19 mortality in landmark trial.
Can semaglutide—the active ingredient in Wegovy and Ozempic—prevent deaths from Covid-19?! It appears so, according to research just published in the Journal of the American College of Cardiology this morning. (Note: I was asked by the journal’s editor-in-chief* to write an editorial that accompanies the remarkable new research paper. Both the new study and my commentary are now available open access on the JACC website, as of this morning.)
Since last year, we’ve known that Wegovy recipients in the SELECT trial had lower cardiovascular disease and all-cause mortality than placebo recipients (the latter finding especially got my attention).
But the researchers conducting the SELECT trial did something rather remarkable in 2020. Instead of stopping their trial when Covid-19 hit—as many trials were forced to do—they kept going and also added Covid-19 outcomes to their study.
By asking patients to report any Covid-19 illnesses to their physicians, the researchers effectively created a double-blind randomized controlled trial that asked whether people who were taking semaglutide during the pandemic fared better if and when they contracted Covid-19. Answer: They did. Among semaglutide recipients, Covid-19 mortality was cut by about 1/3, from 3.1% to 2%. That’s a massive effect, especially given the elevated risks and the average age of the patients (61 years) who reported a Covid-19 illness in the study.
Why did Wegovy (semaglutide) lower Covid-19 mortality?
How did semaglutide achieve this? Well, not by decreasing infections. The rates of reported Covid-19 illness were identical in the semaglutide and placebo recipients. Importantly, the participants who came down with Covid during the study were also similar in terms of their demographics and risks at the start of the trial. So, this finding can’t be chalked up to semaglutide recipients later reporting a Covid illness as having been healthier when the study began. What it does say is that after just a year or two taking the drug, the overall health of the semaglutide recipients had already improved so dramatically that their bodies were already less vulnerable to severe Covid-19. To the tune of a 34% decrease in mortality.
That’s an incredible finding. As I wrote in my editorial for JACC, outcomes from the Covid-19 pandemic in the US would have been much better if our population had entered the crisis with fewer high-risk medical problems. This new research demonstrates that we can actually improve the overall health of higher-risk populations (like those who enrolled in the SELECT trial), and with just a couple of years of treatment.
This is rather empowering information. It also, yet again, should cause economists who think that drugs like semaglutide are not cost-effective for many populations to reassess. Yes, it would be nice if the costs came down, and that will eventually happen. But I maintain that while we know the current cost, but have only just begun to understand the benefits conferred by these important medicines. Remember, the fact that coronavirus infection rates were not affected by semaglutide indicates that the same findings from this study could also apply to the mortality of other dangerous viruses, like influenza or RSV. That is the crux of my essay in JACC.
Conventional wisdom on GLP1s needs to be chucked out the window.
Right now, there’s a conventional wisdom that says that to benefit from semaglutide (and other glucagon-1-like peptide receptor agonists, or GLP1s like it), patients must commit to taking the drugs continuously for the rest of their lives. This is untested and unproven dogma, and I predict it will be overthrown in at least some populations.
Yes, some people who stop taking the drugs gain the weight back. But many don’t! Why spend money on those who no longer benefit from a medication? More than that, why force patients who no longer need it to continue to self-inject it weekly? It’s an absurd notion. While we don’t know which patients will gain weight back if they stop the medications (or cede back other benefits), it’s perfectly reasonable to sort that out by giving all patients a chance to stop taking the medication, once they have reached their health goals. Some may have to get back on the medications. Some may not. That’s fine.
Descending the ladder of risk.
Let’s think further about a group of GLP1 recipients who stop taking the drugs after they’ve been working for some time, but who might have to resume taking them later if their now reduced risks returned (i.e., things like gaining weight back, increases in diabetes blood markers, or the return of high blood pressure). Such “cycling” would not be such a terrible thing. Imagine the situation as analogous to a 10-step ladder; the higher you are, the worse the fall; a fall from over 8 rungs is potentially fatal. Think of a patient who starts out on the most dangerous top rung. Taking semaglutide may be akin to that person slowly descending as many as 7 rungs. So, if after a couple of years, they are on the 3rd rung from the bottom, it would not be the end of the world if they stopped taking the drug to see how it goes. Even if it were found that they slowly crept back up to the 4th or 5th rung after a few years of not taking it, there would be ample time to intervene. Perhaps if they creep back to the 6th rung, it might be worth resuming the drug to lower their risks again. Thinking in this way is a completely sensible approach to preventive medicine. But, currently, this is a third rail in some expert circles.
A metric we need to think about is “days spent in danger.” If intermittent semaglutide use (say, after a period of consistent use leading to measurably improved health status) eliminates the days spent in the danger zone, it’ll be cost and life saving. And, as with some other medications, these “drug holidays,” could even stave off long-term resistance to their beneficial effects.
As the amazing story of the GLP1 drugs unfolds, we’ll continue to discuss what we’ve learned.
If you’ve made it to the end, I hope it’s because you find analyses like these unique and insightful. I’m so glad if that’s the case! How can you support work like this? By upgrading and joining the Premium Subscribers community, if you have not already. Thank you! -Jeremy
Questions? Comments? Chime in! I’m guessing we can get the study authors to engage here—and I’ll try to reach out to them if you have questions I can’t answer.
*Dr. Harlan Krumholz recently began serving as editor-in-chief of JACC. Many of you will know his name from Inside Medicine, as he is a mentor, research collaborator, and great friend to me.
Wow! Fantastic!
Impressive. Thank you