GLP-1s and Nutritional Deficiencies - Part 1 We’re Bringing Scurvy Back?

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I subscribe to a borderline ridiculous number of medical publications from which I receive an absolutely ridiculous number of emails. One headline caught my eye “GLP-1s Bringing Back Scurvy?” Now, those of you who know me know that I’m a parody song…enthusiast, so I immediately started writing lyrics for a Justin Timberlake Bringing Sexy Back parody in my head (We’re bringing scurvy back; these drugs are worrisome and that’s a fact…)

Then I came to my senses and starting clicking. I ended up at an article called “Yes, weight-loss drugs work but nutrition needs attention” published in University News from the University of Newcastle Australia, where the study’s senior author is a Laureate Professor.

In part 1 I’ll talk about this study and article, in part 2 I’ll look at studies that did examine nutritional deficiencies in people taking GLP-1s, and in part 3 I’ll discuss the implications of all of this.

The study that drove the initial article is called “A Systematic Review Identifying Critical Evidence Gaps in Reporting Dietary Change in Randomized Controlled Trials Prescribing Liraglutide, Semaglutide, or Tirzepatide” and Claire Collins is the senior author.

Summary

Research found that only a very small percentage (2 out of 41) of the included Randomized Controlled Trials (RCTs) “assessed and reported dietary intake and quality as outcome measures.” Media about the study, including in direct quotes from the study’s senior author, consistently and uncritically (and, I would add, dubiously) claims that the drugs “work,” but were clear that there is a need for RCTs around GLP-1 use to study nutritional deficiencies.

Deeper Dive

I will say that the articles I read about this study all committed one of my major pet peeves which is talking about a study without linking to it or even giving the name. One author was repeatedly quoted - Claire Collins. I tried some Googling with her name and saw a bunch of articles about the study, some of which mentioned reports of scurvy (a Vitamin C deficiency for which symptoms typically begin occurring after 4 to 12 weeks of inadequate dietary Vitamin C (aka ascorbic acid) intake,) but the study itself didn’t pop up. If this happens to you and you know one of the authors, you can do what I did which is go to ResearchGate.net, search the author’s name, and then scroll to find the study.

The study was a systematic review of research that sought to determine how “randomized controlled trials (RCT) prescribing liraglutide, semaglutide, or tirzepatide assessed and reported dietary intake and quality as outcome measures, alongside weight loss and/or glycemic control.” This is important because these medications disrupt normal hunger both mechanically and psychologically to produce (at least temporary) weight loss. We know that muscle loss is an issue, this study wanted to find out if we know whether or not malnutrition is an issue.

The study is simple enough that it doesn’t warrant an in-depth analysis. Of the 41 included RCTs, the authors found that only 2 “reported or assessed dietary intake or evaluated diet changes secondary to GLP-1/GIP RA medication use.” They identified this as a “major gap in the evidence requiring urgent attention” and I agree.

I want to point out that this has always been an un/under-researched problem. Our healthcare system (in no small part due to infiltration/manipulation from the weight loss industry) has taken a “weight loss by any means necessary” approach that has consistently increased tolerance for harming and killing higher-weight people in efforts to make them thin(ner), under the extremely questionable guise that, if they survive it, they will somehow end up healthier in the end. So while it’s not surprising that this (perhaps not entirely unintentional) oversight is being made, I appreciate these researchers pointing out the problem.

Let’s look at the media article and the way that the senior author discusses the issue. As always, I’ll indent quotes from the article so you can avoid weight stigma and still get the gist of the piece.

It begins

“Popular GLP-1 and GIP medications, such as semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro) and liraglutide (Saxenda) are changing the way ob*sity and type 2 diabetes are viewed and treated. Backed by strong clinical evidence, these prescription drugs can lead to significant weight-loss, improved blood glucose control and metabolic health, and their use is rapidly increasing worldwide.”

This is true as it relates to type 2 diabetes, but the story about weight loss is significantly more complicated. The acceptance and regurgitation of this narrative by publications is an ongoing problem. To make claims like this we really need clear definitions of “strong,” (given the issues that exist with the clinical evidence) and “significant” given that somewhere between about 5% and 15% of people fail to lose even 5% of their body weight on these medications and even more fail to lose even 10%. And that’s before we talk about the issues with the claim that 5-10% weight loss is “significant.”

“But while the focus on weight and health outcomes has been intense, a new systematic review has highlighted a critical blind spot. Very little is known about the exact changes these medications have on what people actually eat, whether vitamin and mineral intakes are adequate, and whether weight-loss achieved through medication also supports optimal nutrition-related health and wellbeing in the long-term.”

This is very well stated and important.

The review examined randomised controlled trials of GLP-1 and GIP receptor agonist medications published over the past 17 years. It found that despite enrolling more than 50,000 participants across 41 trials, only two studies assessed or reported dietary intake data or changes in diet as an outcome.

“These medications work, there’s no question about that,” said study author Clare Collins, Laureate Professor of Nutrition and Dietetics at the University of Newcastle and a HMRI Nutrition & Metabolic Health researcher.

Actually there are questions about that. Even if we define “working” as losing just 5% of body weight (and, again, I think that is a definition without any scientific backing) there are plenty of people for whom it doesn’t “work.” If we define “working” as losing 15-20% of body weight then it doesn’t “work” for about half the people who take the drugs. And that’s just in the short term. The longest study we have so far is a four year study of semglutide which showed only an average of 10% of weight loss (down from 15% in the 68 week trial) and they lost 89.5% of the sample. This endless repetition of what is much more weight loss industry marketing than science is dangerous.

“But a reduction in body weight does not automatically mean the person is well nourished or healthy. Nutrition plays a critical role in health, and right now it’s largely missing from the evidence. With case reports of thiamine deficiency and protein malnutrition, we need to ensure we are not throwing the baby out with the bath water.”

This is accurate and important. What I would point out here is that there is still an assumption that weight loss is a worthy goal and that some form of nutrition therapy can allow people to lose weight and improve health simultaneously and that has not bee proven. Also, let’s remember that, in this case, the “bath water” is a higher weight person’s existence which is concerning (and quite possibly unexamined,) weight stigma.

Weight-loss is not the whole story GLP-1 and GIP receptor agonists suppress appetite and reduce overall food intake. While this contributes to weight-loss, it also raises important questions about diet quality, adequacy of nutrient intakes and whether people are meeting their nutritional needs within lower energy intakes.

The review found that only two trials involving adults reported that they had measured dietary intake, and one was unpublished. Both reported a reduction in total energy intakes, with an altered macronutrient distribution in the medication plus diet group, although it was not significantly different from medication alone. With the methods used to assess diet rated as “poor” or “acceptable”, there is limited confidence in the findings.

This goes back to the need to assess these things. I think it’s worth pointing out that all of these trials - and, in fact, all trials involving these drugs - could have (and I would say should have,) included this in their analysis. I think of, for example the trials I’ve looked at that measured dozens and dozens of secondary endpoints about various cardiometabolic factors but didn’t bother to see if people on the drugs were experiencing malnutrition.

“When people are eating less, the quality of what they eat matters even more,” Professor Collins said.

“If someone loses weight but their diet lacks adequate protein, fibre, vitamins or minerals, that has major concerns for their long-term muscle mass, bone health, brain health, gut health, as well as skin integrity and overall wellbeing.”

This is true, it would also be a dandy time to discuss the existence of weight-inclusive health as an option. It is possible to support health directly rather than using drugs to disrupt normal hunger to the point that people may experience harmful malnutrition.

Health goes beyond the scales Weight is an easily measured outcome, which partly explains why it dominates clinical trials. But these medications and diet quality influence far more than body weight alone, including cardiovascular health, metabolic risk, inflammation and long-term chronic disease outcomes, such as the risk of some cancers.

Again, these drugs may have actual health benefits besides what we know about with type 2 diabetes but the research on these secondary benefits that currently exists has serious issues (I’ve previously written about cardiovascular, joint, and kidney applications as well as offering a framework for analysis of GLP-1s for actual health impacts (rather than weight loss).

Without robust dietary data, clinicians and researchers cannot fully understand the broader health effects of these medications, tailor advice to use of these medications, including in longer-term maintenance usage, nor provide evidence-based guidance to support patients using them.

This is accurate. I will add that without including weight-neutral comparator groups, we don’t have accurate information as to whether a focus on health, rather than body size manipulation, may provide the same or even more health benefits with the same or even less risk.

The review also highlights a broader issue in ob*sity and diabetes research. Diet is often treated as a secondary consideration rather than a core component of metabolic health.

“If we only measure weight and blood sugar, we’re missing a big part of the picture,” Professor Collins said.

“Diet quality, food patterns and nutrient intake all contribute to health. They should be measured with the same rigour as other clinical outcomes.”

I absolutely agree, and I think they need to be measured independent of weight loss.

A call for better evidence, not fewer medications The authors stress that their findings should not be interpreted as criticism of GLP-1 and GIP medications, but rather as a call for more comprehensive research.

This shows the issue here. This article (and, in fact, all of the articles that I read about this) are tripping all over themselves to be clear that they aren’t criticizing the medications. It makes me wonder what they are afraid would happen if they even appeared to be critical of these drugs?

As use of these drugs continues to grow, understanding how they interact with eating behaviours and nutrition will be essential to maximising benefits and minimising unintended risks.

Actually, as use of these drugs continues to grow, understanding how they interact with eating behaviors and nutrition is essential to understanding if there even are benefits that outweigh the risks and/or are benefits greater than can be achieved with weight-neutral interventions.

The review calls for future clinical trials to include validated dietary assessment methods and to report dietary outcomes transparently alongside weight, health and glycaemic measures.

I would love to see this added to trials alongside weight-neutral comparator groups.

“These medications offer enormous potential, but to truly support long-term health, we need to understand not just how much weight people lose, but how well they are nourished,” Professor Collins said.

If we are honest, when it comes to weight loss the reality is that we don’t know if these drugs offer any potential at all. We don’t just need to understand how well people are nourished, but also to understand if not just the side effects but also the weight cycling that are suggested by the current research (and which the weight loss industry is desperately trying to rebrand as “relapsing remitting ob*sity”) actually leave people less healthy for having taken this medication. And I don’t just mean avoiding scurvy.

In part 2 we’ll look at what some studies have found about GLP-1s and nutrient deficiencies.

This month’s online workshop is Weight-Neutral Reproductive Care with Dr. Anna Whelan, MD FACOG. There is a pay-what-you-can-afford option and all registrants get a video. Details and Registration are 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.