How Important Is Predicting Response to Anti-Obesity Medications?

I seldom give a talk on anti-obesity medications (AOMs) where I do not get the question regarding predicting response. Indeed, predicting response appears to be one of those topics that drives much of the enthusiasm around “personalised” medicine (a misnomer, if there ever was one). 

One must first point out, however, that the desire to predict therapeutic response is by no means unique to obesity. In fact, there is probably no area of medicine, where prediction of response is not something that would be preferred. 

Unfortunately, with a few rare exceptions, we are far from predicting therapeutic response beyond statistical probabilities. Thus, in most cases, we present a likelihood, i.e. “you have a one in three chance of losing 20% of your weight”. Whether you would see this as a good or poor chance, depends on whether you are of “glass half-empty” or “glass half-full” disposition. 

Indeed, trying to reliably predict individual responses based on mode of action, pathophysiology or some phenotypical characteristic, has failed miserably (despite all efforts) in most fields of medicine (with cancer perhaps being a notable exception). 

This has not worked for hypertension, dyslipidemia, diabetes, depression, or most other conditions. Indeed, virtually all guidelines recommend starting with the most “popular” medication  (with due consideration of individual indications and contraindications), but then adjusting the dose or adding or switching to another agent based on actual tolerability or response. 

This “trial and error” or rather “empirical” (which sounds much better) approach to medical management is not uncommon in most fields of medicine. Like it or not, predicting who will tolerate and who will respond to a medication remains largely a guessing game. I see no reason why this should be any different for obesity.

The good news is that in medicine we have the luxury of “trying” – something that surgeons don’t have – you cannot try a sleeve gastrectomy – once you have it, there is no going back. 

It is also good news that with all AOMs, early response remains the best predictor of long-term outcomes – so no one needs to continue on an ineffective medication for all too long. 

Yes, it does mean some people will have to bear the cost and exposure to a medication that will not work for them, but, in most cases, there is not much harm done. 

So while, in an ideal world, I would love to be able to precisely and confidently match my treatments individually to each of my patients based on some phenotypical or other characteristic, in reality, much of daily medical practice at the individual level remains largely empirical. What works great for everyone else, may do nothing for you and what does nothing for most patients, may in fact be the best treatment for you – how do we find out? 

We give it a shot! 

@DrSharma
Berlin, D

Disclaimer: I have received honoraria as an independent medical, research and/or educational consultant from various companies including Aidhere, Allurion, Boehringer Ingelheim, Currax, Eli-Lilly, Johnson & Johnson, Medscape, MDBriefcase, Novo Nordisk, Oviva and Xenobiosciences.