A week ago today, we released our Obesity Canada 2025 Pharmacotherapy Clinical Practice Guidelines update (disclosure: I am the lead author).

While it’s wonderful that we now have data to generate recommendations on seven obesity-related health conditions, and more medication choices than we had just a few years ago, there are still so many gaps that need to be filled.   Where does lack of data leave our Guidelines wanting for more?

First, amongst the health conditions associated with obesity that we searched on for potential benefit with weight loss medication, we came up empty handed (or pretty close) on some of them. [Note that there are over 200 health conditions associated with obesity so it wasn’t feasible to search them all; rather, we chose 13 that we felt to be most impactful (see the guideline for details)].  For example, there was not enough (or in some cases no) evidence in people with polycystic ovary syndrome (PCOS), chronic kidney disease, heartburn (GERD) or depression.

We need more data on using combinations of weight management medications.  Just like diabetes and hypertension (high blood pressure), obesity is a chronic health condition that tends to progress with time.  Just as we do for these other conditions, we may in many cases need to add additional treatments over time to continue to control weight and related health issues.  Studies are needed to research how medications may work together to further improve obesity and related health issues over and above the effect of one medication alone.

We need a better understanding of the quality of weight loss (fat vs muscle).  We know that with any currently available weight loss treatment (lifestyle change, medication, or bariatric surgery), around 2/3 of the weight lost is fat, and about 1/3 is muscle.  These data come from DEXA scans which are inherently limited in accurately assessing muscle mass (MRI is better, though way more expensive). And what about the quality of the muscle itself, and what about strength and function? In my view, these assessments need to be routine in clinical trials going forward (more on this here).

Ensuring adequate nutrition is important in any weight loss journey, and especially with highly effective treatments that markedly decrease appetite.  We need data looking at nutritional adequacy, including detailed evaluations of micronutrients during the weight loss journey with medication (more on this here and here).

Fertility and conception planning are areas mostly devoid of data. Can weight management medication improve fertility in women? In men? (more on fertility in men here)  The Catch-22 of studying weight management medication for improvement in female fertility is that pregnancy must be avoided (as weight loss in pregnancy is not recommended, nor do we have safety data on fetal development when exposed to these medications).  But how long should women stop treatment before trying to get pregnant?  Manufactures of some (but not all) medications have given guidance, but this guidance is somewhat arbitrary and differs from one medication to the next (see the guideline under each medication for detailed info).

We also need data to help us know exactly what to do with GLP1-based medication (liraglutide, semaglutide, tirzepatide ) when planning for a surgery or procedure requiring general anesthetic or conscious sedation, in light of the very rare case reports of aspiration (more on this here).

So while we were able to answer a lot of questions and bring great data together into our clinical practice guidelines recommendations, there are many questions unanswered because they need more data…. All topics to look at again in future iterations of this chapter!

Disclaimer: I volunteered my time and received no remuneration for writing this Guidelines chapter.

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