Should everyone be on GLP-1s? What science actually tells us (and doesn't) about the broader health benefits

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The laundry list of possible health benefits from GLP-1 obesity medications seems to get longer by the day. 

They’re proven to reduce the risk of heart disease and improve liver health, and may ward off addiction, too. Mounting evidence suggests these medications might also combat cancer, reducing someone’s risk of developing various forms of the disease. And of course there’s their original purpose: A highly effective medication to lower blood sugar and tackle Type 2 diabetes.

Given all the hype around these drugs, and the rising number of people taking them, it’s easy to assume GLP-1s are a cure-all for, well, almost anything. 

While there’s no question these drugs show immense promise beyond their original purpose, the science is still catching up.

“Should we put these medicines in the drinking water? Should everybody take them? No, not yet,” said Dr. Daniel Drucker, the pioneering Canadian researcher whose lab breakthroughs over the last few decades helped bring GLP-1 drugs to the masses.

“But we are accumulating a substantial body of evidence for disorders where the medicines have benefit — and we’re also learning where the medicines have no benefit — and that’s what guides us in evidence-based medicine.”

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Glucagon-like peptide-1 is a powerful hormone capable of triggering insulin secretion, slowing digestion, and signalling the brain to curb one's cravings and appetite. The class of medications known as GLP-1 receptor agonists simply mimics that natural hormone, including tirzepatide, liraglutide, and semaglutide — the oldest of the drugs, best known by brand names Ozempic or Wegovy.

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Drucker is clear on what we know for sure about their broad health impacts. 

The drugs reduce rates of metabolic liver disease and diabetic kidney disease; they can also cut the severity of sleep apnea and peripheral artery disease. On top of all that, they’re capable of reducing the pain associated with some types of arthritis.

As if that list weren't long enough, Drucker stressed that researchers and drugmakers are also striving to answer just how much GLP-1s could impact cancer and a variety of inflammatory diseases — from Crohn's and colitis to inflammatory skin and lung conditions — as well as “hints from real-world data” that they may curb substance use disorders in a similar fashion to thwarting one's hunger pangs.

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The cancer question is among the biggest, given the disease's prevalence: It’s still the leading cause of death in Canada, and more than four in 10 Canadian men and women will develop some form of it in their lifetime. 

A series of studies presented last month at the American Society of Clinical Oncology, one of the largest gatherings of cancer researchers, adds to a growing body of evidence suggesting GLP-1 use may reduce one's risk.

One paper, published in the affiliated Journal of Clinical Oncology in late May, looked at more than 10,000 medical records and found GLP-1 use among cancer patients was linked to “dramatically reduced” disease progression across multiple types of tumors, including some forms not largely linked to obesity. Breast, liver, colorectal and one type of lung cancer were most impacted, the study found. 

Another headline-making study released at the conference, which also looked at medical records involving roughly 110,000 female patients, found those who took GLP-1s were up to 35 per cent less likely to develop breast cancer than those who didn't take the drug. 

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Lead author Dr. Elizabeth McDonald, radiology professor at the University of Pennsylvania's Perelman School of Medicine, was quick to note that it’s merely an observational study that shows a possible association, not a clear cause, though McDonald does hope to prove the finding through further research.

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One of those pathways is inflammation. It's meant to be a short-term, rapid bodily response to an outside threat, like a fever during an infection.

But it can morph into a long-term, systemic condition — linked to underlying issues like chronic obesity or prolonged stress — and backfire against the body's own healthy tissues.

"We know that having chronic and systemic inflammation is a risk factor for a host of disease," said Dr. Mojola Omole, a breast surgical oncologist at the Scarborough Health Network in Toronto, who wasn't involved in the recent wave of GLP-1 cancer research.

If there are possible cancer-related benefits to being on these drugs, she said, that would be welcome news, given existing cancer treatments can have “very intolerable side effects” for patients.

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Still, she said these kinds of retrospective studies — hopeful as they may be — simply raise more questions than answers.

Knowing for sure what works requires forward-looking research, rather than just looking back at old health data, Drucker agreed. He said only the “gold standard” of scientific research — a randomized controlled trial, where scientists can minimize bias by randomly assigning participants different drug treatments versus a placebo — can prove clear cause and effect.

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While he’s optimistic about GLP-1s' broader health benefits, he said high hopes have been dashed before once scientists move beyond early, observational findings.

Take Alzheimer’s disease, for example. 

“If you look in the registries of people who are using GLP-1 medicines for Type 2 diabetes, whether it was in Scandinavia or in the United States or elsewhere, you would have gotten very excited,” Drucker said. The data from various countries seemed to show people using GLP-1s were diagnosed less often with cognitive dysfunction and Alzheimer’s.

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But that didn’t pan out in clinical trials led by drugmaker Novo Nordisk, where its oral semaglutide drug, Rybelsus, did not significantly slow Alzheimer’s progression when compared to a placebo during two years’ worth of treatments. 

The same thing happened with another diabetes drug, metformin, which showed early promise in preventing breast cancer — at least according to health records and animal studies.

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Then a landmark clinical trial enrolled thousands of patients with high-risk breast cancer, gave them either metformin or a placebo alongside standard treatment, and followed them for five years. “And what did we see?" said Drucker. "Very disappointingly, no benefit of metformin."

Drucker stressed that he’s not sharing these findings to quell excitement around GLP-1s, but rather to encourage more study. It just won’t happen overnight.

“I think the three big buckets of diseases are the substance use disorders, the inflammatory-related disorders and cancer — and those are three enormous buckets that can keep many of us busy for the next five to 10 years."

Senior Health & Medical Reporter

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