Professor Gordon Guyatt Discusses Evidence-Based Medicine, Ozempic Safety, Weight-Loss Challenges & AI-Driven Guideline Evolution

Author(s): Scott Douglas Jacobsen

Publication (Outlet/Website): A Further Inquiry

Publication Date (yyyy/mm/dd): 2025/08/13

Professor Gordon Guyatt is a Canadian physician, health researcher, and Distinguished Professor at McMaster University, widely recognized as the pioneer of evidence-based medicine (EBM). He coined the term “evidence-based medicine” in 1991, fundamentally transforming how clinicians worldwide evaluate research and make patient care decisions. Guyatt has authored or co-authored thousands of influential papers and is among the most cited health scientists globally. He has also led the development of the GRADE framework for grading evidence and guidelines. His leadership, mentorship, and prolific contributions have profoundly shaped modern clinical epidemiology and guideline development, cementing his legacy in global health research.

Scott Douglas Jacobsen: Something I have been noticing the last couple of years, at least in North America, is the public fascination with certain diabetes drugs. For example, while working on a journalism project at a prominent horse facility on the West Coast, I noticed a significant number of higher-income Canadians openly using Ozempic. It was very popular — and some people were visibly losing quite a bit of weight. Some of these individuals could drop from 240 pounds to around 210 pounds. Are these drugs — broadly speaking — safe if people are taking Ozempic or an equivalent?

Prof. Gordon Guyatt: So far, there have been no disasters. But let us wait another twenty years and see what emerges in terms of long-term adverse effects. For now, the data show no significant adverse effects that warrant concern.

However, as I understand it, if you look at real-world use, only about half the people who start these drugs are still on them a couple of years later — so clearly, something is not working perfectly, whether it is side effects, cost, or adherence. But so far, no major safety crisis has appeared.

The big question is whether they reduce strokes, heart attacks, and so on, which we do not yet know. The studies on that are ongoing. There is an early suggestion that they might help, but that is only preliminary.

Now, it is important to clarify: these drugs belong to a class that, in people with diabetes, has been shown to reduce strokes, heart attacks, premature death, and kidney failure. But whether they do the same for non-diabetics who take them purely for weight loss — that is the uncertain part.

Jacobsen: That is a constructive distinction. Theoretically, though — say someone is not taking Ozempic but weighs 240 pounds and loses weight naturally, getting down to 210 or 200 through diet and exercise. Does that, in itself, reduce heart attack and stroke risk?

Guyatt: You mean if they lose weight by eating less and moving more — does that lower their risk?

Jacobsen: Yes — basically, weight loss through lifestyle alone.

Guyatt: The answer is we do not know because not enough people can do it and sustain it for us to study it properly. Randomized trials of dietary interventions typically yield modest weight loss, which rarely lasts. So, bottom line: we do not have enough people who have successfully lost substantial weight and kept it off to know for sure whether it reduces major cardiovascular events in the long term.

Jacobsen: So people are famously bad at losing weight and keeping it off, which means we do not have a reliable sample to study.

Guyatt: Exactly. That is a perfect example of why clinical epidemiology — and medicine in general — can be so challenging. There are big questions for which the data are weak, not because the questions are complicated but because human behaviour makes them practically unanswerable at scale. That is an obvious illustration. 

Jacobsen: You were on the podcast The Truth About Evidence-Based Medicine, and also the Clearer Thinking episode called “Evidence-Based Medicine and Its Discontents.” How are you finding this more frequent public outreach through podcasts and interviews these days?

Guyatt: Oh, it is fun. I have fun talking to you. I also enjoy talking to other people. My whole life has been about believing that I have ideas worth communicating — and the more opportunities I have to communicate them, the better.

Jacobsen: Do you feel that Canada has given you a lot of opportunities — which, of course, you have capitalized on? 

Guyatt: I am the world’s luckiest person! Well, the way I tell my story is this: at the end of my high school years, I had not done any sciences at all — not even introductory courses, let alone advanced ones. Then, partway through myuniversity studies, I decided I wanted to pursue a career in medicine.

I thought, “Oh my god — I am going to have to go back and do all these science prerequisites that I skipped entirely!”However, I soon discovered that there was precisely one medical school in the entire country that would accept applicants without the standard science requirements — and it happened to be in my hometown. So they let me in.

Jacobsen: That is a very Canadian story!

Guyatt: Wait until you hear the next part. After that, I completed my internship — what we now call PGY-1 — in Toronto and then returned to McMaster for my second year of training. I joined the chest diseases program. In the final year, they wanted every trainee to do physiological research. I had no interest in physiology research, but I needed to fulfill the requirements. So, I persuaded them to let me pursue a master’s degree in Clinical Epidemiology instead.

At the time, I was not particularly interested in research, but it was a better option than physiology. So I did it — and thenI thought, “Oh! This is interesting stuff.” I realized I might want to keep doing it. And, as luck would have it, I happened to be in the best place in the world for clinical epidemiology — right in my hometown.

It was a complete coincidence, but I was surrounded by extremely bright, innovative, collegial, and supportive people. That is what made McMaster the best place for this kind of work. So, I always say: I stumbled into the best possible place, by chance, in my backyard — and I benefited from absolutely superb mentorship.

When people ask me about my research career and how to be successful, I always say that the most critical factor is mentorship. I had multiple excellent mentors who made all the difference.

Guyatt: My primary mentors were terrific people. Some were in the U.S., but I was fortunate to be in an environment at McMaster where, for example, my primary mentor was a statistician — and there were other excellent statisticians around as well. I also had strong statistical mentorship. Anyway, my story is: luck, luck, luck, luck, and more luck!

Jacobsen: So, do you feel a sense of wanting — or needing — to give back, given the opportunities you have had?

Guyatt: Oh, of course.

Jacobsen: How do you find communicating to the general public, as opposed to giving an academic lecture or workshop?

Guyatt: Honestly, I have not had many opportunities to communicate directly to the general public. I suppose I have not actively sought those opportunities, and they have not exactly fallen into my lap either — though I have done a few on occasion.

But when I do, there are always interesting challenges — positive challenges — about how to communicate complex ideas. For instance, explaining why randomized trials are so important and what the limitations are of non-randomized observational studies.

So I often use an example: What is the impact on your risk of dying of being in the hospital? If you do a study, 10% of hospitalized people die during the study period. In contrast, only 2 out of 1,000 people in the community die in the same period. So, you conclude: Being in a hospital is dangerous — if you want to stay healthy, stay away from hospitals!

Everybody laughs. But it makes the point: the people who are in the hospital are fundamentally different from the people who are not — that is why the mortality is higher, not because the hospital is killing them.

Then, if I switch to something like antioxidant vitamins, people struggle more to make the same leap. They do not immediately see that the people who take antioxidant vitamins might differ systematically from those who do not — and that difference, not the vitamins, could explain the outcome.

So, I would like to start with the hospital example to establish the concept: Perhaps it’s not the intervention itself; maybe it’s something about the people receiving the intervention.

Another example I often use is about autism and vaccines. Ninety-nine percent of kids who develop autism have been vaccinated. So, someone argues that vaccines must be causing autism! But what is wrong with that argument? Well, ninety-nine percent of kids without autism have also been vaccinated — so you are comparing apples to apples. You need a valid control group to interpret it correctly.

I have been surprised. When I use the hospital example — everyone immediately gets it. But when I say, “Ninety-nine percent of people with autism have been vaccinated — therefore, vaccines must cause autism,” and I pose this to a medical audience and ask, “What’s wrong with this?” — they do not immediately jump up with the correct answer.

Recently, I have been using more examples I developed for the general public with medical audiences as well. They can all tell you, in theory, that randomized trials are a good idea. Still, when it comes to recognizing the logic in specific real-world examples, it is sometimes harder for them to make the connection.

Jacobsen: That makes sense. All right — here are a few softballs to wrap up. What do you see as the biggest challenges for implementing living guideline methods globally?

Guyatt: The number one challenge is having enough people with the necessary skills. Number two is continuing to educate people about why living guidelines are desirable.

And then, very practically, you need the resources and the institutional commitment: you need a team ready to update recommendations quickly when new evidence emerges, you have to pay them, you have to train them — and you have to get organizations to commit to this approach over the long term. All of that together is a big hurdle.

Jacobsen: Good point. We don’t need to delve into AI again, but I did ask this a while back. It might still be the same: In terms of methodologies beyond network meta-analysis, could big data or AI realistically advance that frontier — at least in theory?

Guyatt: Big data, no — because big data cannot solve the fundamental problem of distinguishing whether an outcome is due to the intervention itself or due to differences in the people receiving it. So, big data analyses have the same inherent limitations as any non-randomized observational study.

Where AI will be a big help in two areas: first, in interpreting images — radiology, pathology, all of that — and second, in the processing of evidence, for what I do, AI is going to make the synthesis and grading of evidence much more efficient.

Jacobsen: Not as a media person per se, but something I have noticed: when people want to frame something positively, they often talk about “the community.” But when they want to demonize a group, they say “they.” For example: “They — the medical establishment — did this or that.”

Internally, as a positive, we often say, “We, the medical community.” But in reality, it is people, and people are individuals — it is not a monolith. So, with that in mind, if you had one call to action for the global EBM community, what would it be?

Guyatt: I would say this — especially to EBM educators: Realize that virtually no graduate will ever read the methods and results sections of an original research article once they leave training. So, gear your educational strategies to that reality.

Jacobsen: That is so practical — and so true. One more, just for fun: What are your favourite Clin Epi aphorisms or quotes — or even just general medical sayings?

Guyatt: Well, there is a classic Clin Epi one. There is always the exact correct answer to every Clin Epi question — and it is two words: “It depends.”

Jacobsen: [Laughing] That is perfect. I love that. That is always a good response! Thank you so much for your time again, Gordon. 

Guyatt: Cheers. Bye-bye.

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