In Part 1 we started discussing the study Two Years After Stopping GLP-1s, Most Patients Sustain at Least Some Weight Loss by Bartelt et al. which I identified as possibly the worst, and definitely among the top 3 worst, studies I’ve ever analyzed. In part 1 we talked about the platform (Epic Research), the researchers, and the basic methodology for reporting. Today we’re going to get into the analysis. Remember that there are two sources, the first is the actual article, the second is what I am calling the supplementary materials that is a pdf that is linked (though not at all clearly) in the article. We’ll compare the claims made in the article to the data shown in the supplementary materials. I think as we get into this it may be helpful (and maybe just a bit comforting) to remember that this was not published in a peer reviewed journal - it’s Epic publishing Epic’s research on Epic’s website. We’ll begin with the most basic claim: “we studied 188,722 patients who stopped using a GLP-1 medication after being on it for at least 90 days and who lost at least 5 pounds while on it.” You might be thinking “wait - in Part 1 you said the study population was 323,782, what happened to the other 135,060 people? Let’s go on this journey together. We’ll start by looking at their data. In the supplementary materials, Table 1: Characteristics of the Study Population looks like this: So they say in the article that they studied 188,722 patients but the very first line of the supplementary materials chart about the study population says that the total number of patients was 323,782. But it gets a bit weirder, if you add up all the participants in the different age categories you get 323,750, 32 short. If you add up the totals across the drug groups you do get 188,722, if you add up the participants in the weight loss category you get 323,782. If you add up the diabetic status you get 323,782. What is going on here? Maybe they originally looked at 323,782 records of which only 188,722 were not excluded for some reason, and maybe 32 of the participants did not have an age on their electronic health record? At least the number of people across the drug groups in the supplementary materials chart matches the number of people they claim to have studied but this is, in the absolute more charitable description, an extremely confusing way to present this data. In part 1 we discussed the fact that the inclusion criteria were not particularly stringent but the biggest issue, to me, is that the researchers appear to have just done calculations with whatever data they happened to have, but reported it and drew conclusions as if they had consistent data on all participants. For each of the three drug groups (semaglutide, liraglutide, tirzepatide), they present an interactive graph that shows “the proportion of patients by amount of weight regained or lost after stopping [liraglutide/semaglutide/tirzepatide].” Let’s dig in. In the article we find Figure 1 - Proportion of Patients by Weight Change After Stopping Semaglutide we can see in the lower left “n=139,972 patients.” But if you look at the supplementary materials you find Table 2 Proportion of Patients by Weight Change After Stopping Semaglutide. This is the table from which they are drawing the data for Figure 1. The final column of the supplemental table is “patients” and the number in that column represents the number of the original 139,972 patients who had taken (and subsequently stopped taking) semaglutide for which the researchers had a weight at each month of their calculation. At month 1, the researchers had a weight for 68,754 of the patients and this number trends steadily downward until month 24 when they only had weights for 2,650 of the original 139,972 patients. At literally no point does Figure 1 in the original article give data for the n=139,972 patients the label claims. In the liraglutide group the graph in the article says n = 23,377. The supplementary tables show that in month 1 they had weights for 11,580. That steadily declined until month 24 they had weights for 1,268 of the population. In the tirzepatide group, the article says n= 25,373 patients. At month 1 they had weights for 12,909 patients which steadily declined until at at month 24 they only had a weight for 145 people (that is not a typo, they were doing the two year calculation upon which they drew their bold conclusions with only one hundred and forty five of the original 25k+ people represented!) This is such a bonkers way to do this that I actually emailed them, using the semaglutide table as an example, to make sure I was understanding this correctly. They assured me that I was: “Yes – there were 139,972 total patients on semaglutide who met the conditions in the study cohort. The patient count in Table 2 represents the number of patients that had a weight reading in a given month, so patients can be represented in multiple months.” So let’s discuss the “key findings” At 24 months post-cessation, 56% of semaglutide, 52% of liraglutide, and 55% of tirzepatide patients kept the weight off or lost additional weight. Complete weight regain occurred in 23% of semaglutide, 21% of tirzepatide, and 27% of liraglutide users at 24 months. Weight trajectories stabilized after 12 months, with only small variations in the distribution of weight outcomes through year two. Remember that when they state these 24 month findings (or when in the title they say “Most Patients Sustain at Least Some Weight Loss,”) these statistics are drawn from information for only 1.9% of the semaglutide group, 5.4% of the liraglutide group, and 0.57% of the tirzepatide group. When they say kept the weight off or lost additional weight, subjects would qualify if they maintained 1% of the weight they lost. EDIT - I’m adding this paragraph for additional clarification based on a great comment below. If you look at their percentages, it can seem like a lot of people didn’t regain weight. For example in the Semaglutide group, for example, at 1 month the “doubled their weight loss group” was 5.01% of 68,754 participants. That’s that’s about 892 people which is 0.64% of the original 139,972 people. At 24 months it was 25.89% of 2,650 people. That’s about 686 people which is about 0.49% of the original 139,972 people. As I mentioned in part 1, we also don’t know if this miniscule percentage of the total group even actually stopped taking the drugs, or if they started getting them from a different source that did not add them to their medical chart. What happened to the 98.1% of the semaglutide group, 94.6% of the liraglutide group, and the staggering 99.43% of the tirzepatide group for whom the researchers did NOT have a weight at 24 months? Is it more likely that people who were regaining weight did not come back to get weighed in? These researchers have absolutely no idea and they don’t seem to care. (They said that weight trajectories stabilized at 12 months so even if we look at the data at 12 months they only had weights for 12.7% of the semaglutide group, 18.5% of the liraglutide group, and 8.1% of the tirzepatide group.) Under limitations they state “We allow a patient to be included in each month, using their highest weight in that month. Patients who have repeated weight measurements might be the extremes of weight change.” Gentle readers, I would say that this is the least of their limitations. The fact that they are stating these incredibly broad conclusions about weight regain (including in the title!) based on a tiny fraction of the data they’ve led us to believe is included, and that they AT NO POINT disclose any of that in the main paper is, to me, unforgivable. Horrifyingly, in researching this piece I found other studies that actually cited this one so I’ll end this by saying that this study completely lacks the academic rigor or appropriate methodology necessary to be used to counter research showing high rates of weight regain after GLP-1 cessation. GLP-1s are being taken by a huge percentage of people and being prescribed (and in some cases pushed) by many prescribers, research like this has the potential to do incredible harm by generating blatant misinformation. We have to do a whole lot better than this. This month’s online workshop is How to Be Your Own Medical Advocate. You’ll learn strategies to advocate for yourself to help you get the evidence-based, compassionate, healthcare you deserve, and what your options are if you don’t. There’s a pay-what-you-can option to make sure money isn’t a barrier and all registrants get a video in case you can’t make it live. Details and registration are here! If you appreciate the work I do here, you can support my ability to do more becoming a free or paid subscriber! Liked the piece? Share the piece! More researchThe Research Post More resourcesThe Resource Post *Note on language: I use “fat” as a neutral descriptor as used by the fat activist community, I use “ob*se” and “overw*ight” to acknowledge that these are terms that were created to medicalize and pathologize fat bodies, with roots in racism and specifically anti-Blackness. Please read Sabrina Strings’ Fearing the Black Body – the Racial Origins of Fat Phobia and Da’Shaun Harrison’s Belly of the Beast: The Politics of Anti-Fatness as Anti-Blackness for more on this. Get full access to Weight and Healthcare at weightandhealthcare.substack.com/subscribe
