GLP-1s and Cancer Part 4 - Three Studies
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In part 1 we talked about the basics of the studies around GLP-1s and cancer. In part 2 we looked at a study of relatively early data around breast cancer. In part 3 we began discussing a Guardian article that made broad, unsubstantiated claims about these drugs and cancer. Today, in the final part of this series, we’ll take a look at the three studies the Guardian author quotes. Before we do that, if you haven’t read part 1, I recommend doing so as we discuss the issues that arise with these studies at length.
As we wrap this up, I want to give a shoutout to my paid subscribers! Of course I’m grateful for everyone who reads this, whether you just found it, are a a free subscriber, or a paid subscriber. That said, this series took hours of research and paid subscribers provide the support for that work, so thank you!
One thing I noticed was that each study is related to the American Society of Clinical Oncology (ASCO), particularly their annual meeting. So I did some digging and the sponsors for this meeting (through the ASCOs foundation) include Eli Lilly, manufacturer of GLP-1 Tirzepatide (Mounjaro for type 2 diabetes, Zepbound for weight loss,) and Genentech which has a GLP-1 in active development.
Summary
The Guardian quotes three studies. One of them was published after the Guardian article was written and still doesn’t exist in its final form. Two have not been peer reviewed or published and were presented at the ASCO meeting. A number of the authors across the three studies have conflicts of interest with the drug manufacturers. They are all retrospective cohort analyses and thus none of them can determine that GLP-1s have an impact on cancer. None of them include income as a possible confounding variable which is a significant limitation.
Ok, let’s get into this. The first study they refer to is:
GLP-1 Agonists Are Associated With a Significant Reduction in Breast Cancer Incidence in Women, by Elizabeth S. McDonald et al.
This paper was accepted for publication by JCO Oncology Practice which is the journal of the American Society of Clinical Oncology, but is so new that the full study is not yet published in its final form. It’s currently a PDF with large markings indicating “Accepted Unedited Manuscript.” Interestingly, this study was only published online on June 5 and The Guardian article was published June 2. There is a disclaimer that includes “Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to JCO Oncology Practice remain”
The current manuscript does not have information about the funding of the study or the disclosures of the authors that I could find. However, the study was presented at the ASCO meeting where disclosures were published. The only author listed on the study whose disclosures are NOT included in the ASCO meeting disclosures is John B. Buse, but we’ll get to that. For each author I’ll list the ASCO meeting disclosures and what I found in the OpenPayments database between 2018 and 2024.
Elizabeth McDonald
No Relationships to Disclose
Nothing found in OpenPayments
Laura Gillis
No Relationships to Disclose
Nothing found in OpenPayments
Peter Gabriel
Disclosures:
Honoraria - National Comprehensive Cancer Network
Consulting or Advisory Role - Layer Health
Travel, Accommodations, Expenses - National Comprehensive Cancer Network
(OPTIONAL) Uncompensated Relationships - Epic Systems
Open Payments:
Peter Gabriel has taken 14 food and beverage and travel and lodging payments from Eli Lilly which are not mentioned in his disclosures. While they total only $659.95, they do suggest that he has received a lot of “training” from them and research shows that payments less than $20 can impact the behavior of physicians.
Kham Xapakdy
No Relationships to Disclose
Nothing found in OpenPayments
Anthony Young
No Relationships to Disclose
Nothing related found in OpenPayments
Mitchell Schnall
No Relationships to Disclose
Nothing related found in OpenPayments
Etta Pisano
Disclosures
Patents, Royalties, Other Intellectual Property - I have several patents, none of which have paid me any royalties.
Travel, Accommodations, Expenses - University of Ci; Washington University School of Medicine
Nothing related found in OpenPayments
Remember that this is the only author who was not listed in the ASCO meeting disclosures
That is interesting because he has the most significant conflicts of any of the authors
$517,037.93 in general payments (with Novo and Eli Lilly as his top patrons)
$7,799.28 in Research Payments (with Novo Nordisk second to Sanofi-Aventis)
$3,599,695.93 in Associated Research Funding (with Novo as the top patron by far with $2,863,267.10)
On to the study.
This was another retrospective cohort analysis (the limitations of which we discussed at length in Part 1). They looked at the health records of 111,646 cis women from 45-80 years old with a BMI of 25 or greater. They “performed one-to-one, case-control matching using propensity scores based on age, race, ethnicity, highest BMI, breast density, and history of type 2 diabetes.” Here again there is a failure to consider income and, again, the ability to access GLP-1s may in fact be standing in for income that allows for other lifestyle factors that may account for cancer differences.
They defined GLP-1 use as “first prescription prior to the exam date” which is pretty non-specific. People could have been on these drugs for years or just weeks prior to the exam. Additionally, as in other studies we’ve looked at in this series, they don’t take into account what drug participants were on, or what dose of the drug they were taking.
The outcome they were looking at was detection of breast cancer.
Throughout the study the authors seem to be trying to generate assumptions that the differences in outcome are due to weight, but what they actually found was that “GLP-1 treatment was associated with a lower incidence of breast cancer, independent of age, race, ethnicity, BMI, breast density, and diabetes.” (emphasis mine) and they don’t seem to have data to even know if patients lost weight. The authors are clear that “Findings support the need for prospective trials investigating GLP-1 agonists for breast cancer prevention.”
In their conclusion section they are honest that “While our results are intriguing, they are largely hypothesis generating.”
But then they end their “conclusions” section with “There is perhaps no singular preventative intervention with such broad potential to improve women’s health” which isn’t so much a scientific conclusion as something that you might say if you got millions to research these drugs, but that’s just me spitballing.
That said, as I’ve said before in this series, and especially given that the association they found was independent of BMI, I find it troubling that they are confining their research to higher-weight people when lower-weight people also get breast cancer and also take GLP-1s.
The next study is:
Real-world survival benefit of glucagon-like peptide-1 receptor agonists (GLP-1 Ras) concomitant with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy in hormone receptor-positive (HR+)/HER2− metastatic breast cancer: A large propensity-matched analysis.
This study does not appear to be peer reviewed or published so the full information isn’t available. It appears to have been presented as a poster session for the American Society of Clinical Oncology and the only information I could find was from that abstract.
While the information available is fairly short, the disclosure section is not, with the following authors disclosing conflicts of interest:
Michela Palleschi
Disclosures:
Honoraria - Gilead Sciences; Novartis
Research Funding - Pfizer (Inst)
Travel, Accommodations, Expenses - AstraZeneca; Lilly; Novartis; Pfizer
Caterina Gianni
Consulting or Advisory Role - Novartis
Research Funding - Gilead Sciences (Inst)
Travel, Accommodations, Expenses - Gilead Sciences; Ipsen; Pfizer
Filippo Merloni
Honoraria - Gilead Sciences; Lilly; Novartis
Travel, Accommodations, Expenses - Pfizer
Alberto Farolfi
Honoraria - Abbvie; AstraZeneca; GlaxoSmithKline; MSD Oncology; Pharma&
Consulting or Advisory Role - Abbvie; AstraZeneca; Eisai; GlaxoSmithKline; MSD Oncology
Travel, Accommodations, Expenses - Abbvie; AstraZeneca; MSD Oncology
Antonino Musolino
Consulting or Advisory Role - Daiichi Sankyo/Astra Zeneca; Eisai Europe; Lilly; Novartis; Seagen
Research Funding - Lilly; Roche (Inst)
Travel, Accommodations, Expenses - Pfizer
From the abstract we can see that this is yet another retrospective cohort study and, again, the author is making assumptions about weight/weight loss and cancer that ignore possible confounding variables and without any actual information about weight loss in their study population.
They used the TriNetX Global Collaborative Network (we discussed the limitations of this in Part 2) and identified patients with metastatic Breast Cancer “receiving endocrine therapy (ET) plus a CDK4/6i: 26,689 patients treated with ET+CDK4/6i alone and 604 patients who also received a GLP-1 RA initiated within 3 months of CDK4/6i start.”
This study is a good example of the need to study complexity - there are many types and subtypes of cancer and many treatments all of which might impact or be impacted by GLP-1s…or not.
The propensity matching included “age, race, body mass index, heart failure, hypertension, diabetes mellitus, fulvestrant use, and type of CDK4/6i” but again this study did not include income, the issues with which we’ve discussed repeatedly through this series.
After propensity matching “604 matched pairs of patients were identified in the ET plus CDK4/6i and GLP-1 RA groups, respectively with well-balanced baseline characteristics.” Again, we don’t have the full study so we can’t get any more information than this.
Their results speak to the overall survival rate. There was a mean follow up of about a year and four months (though their Interquartile Range (IQR) of 24.5 means that the spread of follow up time was wide.) The median overall survival rate for those taking GLP-1s was 67.9 months compared to 49 months for those not receiving GLP-1s. Here again, we don’t actually know if it was the GLP-1s or a confounding variable that was not accounted for (like income or access to healthcare, as we discussed in Part 1) that made the difference. We also don’t know the quality of life over those additional months (which may or may not be important to those with this diagnosis).
Finally, we know that the GLP-1s were initiated within three months of these patients being started on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) but we don’t know what drug, what dose or, if we want to be honest, if the patients even took the medications because the study is just pulling prescription data from previous medical records.
Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors
The third study they discuss is also not yet published. It was also presented as a poster session for the American Society of Clinical Oncology.
We’ll start with the disclosures. Only one of the authors (the last author, who is often the senior author,) disclosed conflicts:
Jaroslaw Maciejewski
Consulting or Advisory Role - Alexion Pharmaceuticals; Bristol-Myers Squibb/Celgene; Geron; Novartis
Research Funding - Alexion Pharmaceuticals (Inst); Apellis Pharmaceuticals (Inst); Apellis Pharmaceuticals (Inst); NIH (Inst); Novartis (Inst); SOBI (Inst); SOBI (Inst)
Open Payments Shows:
General Payment Records $235,065.28
Research Payments $15,065.90
Associated research funding $3,808,798.58
With Novartis his top patron
This is another retrospective cohort analysis using TriNetX Global Health Research Network.
They included seven cancers (breast adenocarcinoma, prostate adenocarcinoma, Non small cell lung cancer (NSCLC), colorectal adenocarcinoma (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and pancreatic adenocarcinoma) and included patients with “Stage I-III cancer who initiated GLP-1RA therapy after diagnosis.” There is no information as to what drug, what dose, or how long after diagnosis therapy was initiated.
The primary outcome they were considering was progression to Stage IV and they included a secondary outcome of overall survival.
They compared those on GLP-1s to those on DPP-4 inhibitors which is another class of Type 2 Diabetes medication including Jenuvia and Tradjenta (note that they didn’t compare them to SGLT2 Inhibitors which, as we saw in a previous study, showed the same results as GLP-1s.) The propensity matching included “demographics, BMI, glycemic factors, smoking, comorbidities, screening frequency, oncologic treatments, and concurrent medications.” It’s not clear if “demographics” included income but so far none of the retrospective cohort analyses using TriNetX have included income.
They found that the GLP-1 group had reduced metastatic progression in 6 of the 7 cancers, though it was only statistically significant in four (NSCLC, breast, CRC, and HCC) meaning that for the other cancers, it’s just as likely that the difference was due to chance as due to GLP-1s.
I have a number of questions about this study that I can’t answer because it’s not published, but they were clear in their conclusion that “These findings warrant validation in prospective randomized controlled trials and mechanistic investigation of potential antineoplastic pathways driven by GLP-1RAs.”
I agree with them, there should be actual trials and until there are, reporting as was done in the Guardian (and, some readers have mentioned other places like NPR) must be done responsibly and that isn’t happening.
As I wrap up this series I want to acknowledge that cancer is terrifying. It would be understandable if someone facing one of the diagnoses in these studies felt like it would be worth it to try a GLP-1 drug and I believe strongly in the bodily autonomy they have to make that choice. That said, it’s a tough choice because there is no information as to what drug, at what dose, taken when/for how long will actually make a difference, or even if it will make a difference.
I hope that instead of continuing to pump out retrospective cohort analyses that all have similar limitations, we’ll see some actual trials that can give us real, actionable information. At this time I could not find such a clinical trial that is happening right now which makes me worried that, rather than taking a chance on finding out in a clinical trial that GLP-1s don’t have an impact on cancer, Novo Nordisk and Eli Lilly are happy to let the “but there’s so much evidence” fallacy take the place of the actual evidence that we would need to have actionable information to practice ethical, evidence-based medicine.
It’s happening tonight (and there’s a recording if you can’t make it!) The weight loss industry is up to shenanigans that impact the healthcare of higher-weight people. Louise Adams and I are teaming up for this month’s online workshop - Exposing the Weight Loss Industry’s Secrets and Tricks. We’ll talk about what they are doing, why they are doing it, and how we can pushback. All registrants get access to a video and there is a pay-what-you-can-afford option so that money isn’t a barrier. Details and Registration here!
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*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.
Reading the last study, where people started glps after diagnosis, made me think about how difficult cancer and treatment for cancer is, and then adding the side effects of glps on top of that sounds awful. Cancer patients deserve better than this. Posters are great, but they aren't a peer reviewed article.
This was a great read, and pulling each author's OpenPayments record against their ASCO disclosures is the kind of legwork these write-ups almost never do.
The detail that stuck with me was your note that SGLT2 inhibitors showed the same association in an earlier study, yet this one only benchmarked GLP-1s against DPP-4. When two mechanistically unrelated drug classes both 'protect,' the shared variable is usually the patient who gets prescribed either one, not the molecule. That, plus the breast cancer signal holding independent of BMI, makes the weight-loss story the discussion sections reach for hard to sustain.