WHY IS EVERYONE TALKING ABOUT RETATRUTIDE?

Mechanistic action & context that’s super important

Now I don't want to dive right into the uses of retatrutide and how this could be applied in certain contexts, without giving some background context to the mechanism of action, what this drug actually is and why I believe this compound has truly become the hottest product in the world of performance, longevity and ‘health’. It feels like this has become the injectable, adult equivalent of kids breaking the legs of other kids trying to buy their favourite flavour of that gash ‘PRIME’ energy/hydration drink that is now seemingly taking up more shelf space in your local B&M than it is being purchased by parents absolute desperate to nail their child’s christmas present.

It’s one that has heavily split the crowd as we continuously see two camps- “this is cheating, you guys are lazy and are forever looking at shortcuts” OR “shut up judging people, why wouldn’t you take a shortcut and something that will make us better in the long run”. My job is not to sway you into either of these camps, frankly I don’t mind whichever side of the fence you sit on! Science is nuanced, progressive and we’re so incredibly fortunate to have discussions that encompass a great deal of nuance. So please take this article not as an attempt to convince you one way or the other, but as a resource. It could be used as a platform to further your understanding of a realm of science which is progressing at an incredibly rapid rate. It could offer a lifeline to millions of individuals who wish to perform behaviours that may offer a better quality of life and it might create a landscape that we deem impossible at present. SO THE MECHANISMS OF ACTION THEN, THE COOL SCIENCE STUFF: What appears to have set this compound apart from other drugs of a similar realm, is its ‘triple action’:1) We are firstly seeing a GLP-1 agonist. Remember when the world lost its mind when Kelly Osborne announced her dramatic transformation following the use of ‘Ozempic’? And apparently ‘the gays’ discovered jabbing yourself isn’t so bad? This is what we’re referring to here. This is what is more typically characterised by the slowing of gastric emptying times, a lowering of postprandial glucose and in my opinion, the predominant driver of appetite suppression. This is the feeling of being fuller for longer and the thing that most tend to claim leads to significant reduction in caloric intake due to all of the above. Note- this is ONE receptor/signal/pathway that we are seeing.

2) Second up, we’re seeing another player enter the discussion. Glucose Dependent Insulinotropic Polypeptide (GIP for short, we don’t need to use its Christian name here do we). So this one’s an interesting one and could be regarded as a ‘development’ from just the use of the above. This is the Mounjaro that has also made some pretty big waves within medicinal context & private prescriptions at present. This is often discussed for its ability to ALSO provide that appetite suppression but without the commonly associated nausea (I don’t personally agree entirely with this statement but i agree that we’re seeing action on a great host of cascades). This is actually pretty decent at potentiating insulin in nutrient-fed states so could be argued to complement the above GLP-1 agonist to produce ‘better’ glycaemic control. If I had to use an analogy, I'd say Ozempic is a trike and Mounjaro is a bike. You’re likely going to get to your end point significantly quicker and less trashed with the use of a bike, than a trike. 

3) And finally, we have the thing that arguably sets this drug apart- Glucagon receptors. I’d argue that this is the element that sways most to utilise the compound, due to its effects on lipolysis (pretty much translates to ‘breakdown of stored fat’, just as a very simplistic explanation). It can influence hepatic glucose output, which if I were to summarise in the style of Arnie, it would sound something like “LIVER YOU MUST BURN FAT AND DUMP ZEE GLUCOSE, NOOWWWW”. Within clinical trials, we’re seeing this favour net weight loss and improvements to blood glucose control.

Is this really just another fat loss drug that we should be looking to argue about?

In a word, no. That’s it, that’s the section.

Alright I'm not that much of a reductionist really. This is a drug that I believe shouldn’t be painted with the same brush. If I were to summarise the world of ‘fat loss drugs’ into two columns, it would be something like:1) the ones that obliterate appetite2) the ones that feel like you’re being chased through lidl by a karen who wants that last loaf of tiger bread that you’ve got in your basket.

The issue with compounds like these is that we can see a rise in stressors that can blunt beneficial behaviours and sometimes a bit of a ‘muting’ of physiology. Now this is not a blanket statement for all compounds and all candidates, but it’s a statement that needs to be made as it has been observed for quite some time in an array of demographics.

Though we have seen the meteoric rise in what have lovingly been named ‘skinny pens’, in this instance, I believe it branches out further than its ability to potentially suppress appetite or ramp up sympathetic nervous system activity.

Rather than just seeing a reduction in caloric intake, as a result of the changes to gastric emptying times and hunger cues, this acts on receptors and signalling which lead to downstream changes to nutrient handling IN ADDITION to changes to that classic ‘food noise’. I say this with inverted commas as this looks/sounds/feels different for everyone, and I'm not about to be someone that validates what your relationship with food does or doesn’t look like. I believe Retatrutide use can result in fewer occurrences of dopamine-based food hunting and just a little less oscillation in feeding desire but it’s incredibly important to note that these behaviours look very different in each individual, so your inter-individual response is what’s important for YOUR context. You’ll have heard me say this before, but n always =1. 

Why appetite suppression might be the worst thing you could be hunting down right now

As with any argument, there’s always a caveat. It sounded pretty flawless up until this point didn’t it? I’m afraid that’s not how we communicate when trying to illustrate the importance of scientific application and the intricacies of research compounds making their way into the public eye.

Humans are biological systems and we’re actually incredibly demanding if you consider all of the things that we try and juggle as adults. Have you ever seen those memes that have a picture of some worn out, hungover and blood shot eyed lass on the street that say ‘me trying to drink enough water, sleep, stay off my phone, exercise, eat fruit and veg, be sociable, rest’ etc? Well that’s not really dissimilar to how the body can feel when certain areas are really ramped up and others are suppressed. Though data on habitual diet isn’t as thorough as we have seen in other drug use, it has still been reported that there are cases of malnutrition associated with the use of these compounds. Which truly, isn’t that surprising given we are actively attempting to reduce caloric intake and subsequently we may begin to see deficiencies in certain nutrients. There will be a host of demographics who perhaps don’t regard their nutrition as something they look at with a magnifying glass, but in an athletic context, this is a pretty big lever for us to pull.I’m a huge believer in RESPECTING appetite and using it as a piece of feedback that allows you to pull some of the levers that I mentioned earlier.

Satiety is very much a tool and if we play that card to the extent where nutrition becomes lacking in several areas, we’re going to see some pretty negative implications on performance; and damn, i’m a performance coach so for people like me, this is a fucking nightmare. 

So is this cheating and why are people apparently SO FUCKING LAZY for using this?!

Is this clickbait? Did I finally make it as an influencer? These are things that are said quite frequently about the likes of Ozempic, Mounjaro and Reta so I'd argue it’s not clickbait at all! I do find it to be a bit of an emotionally charged elephant in the room and I believe the best way to approach this, as always in my geordie, non problematic & diplomatic state, is with nuance and understanding. This is a topic that really blew up on my instagram Q&A, and is honestly one of the main reasons this article has taken the form that it has.Here’s my take: there’s a huge difference between outsourcing effort and enhancing physiology. Now I'm very willing for a lot of the ‘earned not given’ crowd to come at me on every single one of my social platforms, but hear me out before you call me a tosser. If someone is choosing to use a drug as a substitute for some pretty basic and essential behaviours, then yep, fine i’m really going to be in your corner and agree that perhaps the lazy comment has some credence. I’d agree that the drug is not necessarily teaching you anything, if you regard it as something that 'lets you eat shit and not get fat’. And sure, maybe we will see a return to some really destructive behaviours following their use, because there was almost a lack of respect for the application of this drug. Let’s say someone has quite a chaotic relationship with food and in order to ‘fix this’, retatrutide is deployed so that it forces that blunted appetite response. I’d argue this isn’t exclusively a solution. Regarding it as a tool that may enable more education around behaviours and then allow for those beneficial behaviours to take place, is where I believe this drug will offer the most benefit. I believe the basis of this comment is coming from a lot of us seeing more cases of people ‘boasting’ they didn’t need to diet or perhaps perform any formal cardio, in order to see the changes to body composition that others are pining for. Which as i’m sure we can all agree, is absolutely fucking backwards

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So who should actually consider this drug?

You partaking in the use of a drug like Retatrutide, is not for me to decide in ANY CAPACITY. But what I can do is give some theoretical scenarios and candidates that may or may not find benefit in using this drug.

If someone is incredibly competent with nutrition, has a degree of consistency and understands what it means to be nourished, then I’d argue they’re better placed to implement it without seeing some of the aforementioned drawbacks. These are also typically the individuals who are more used to tracking autonomic and anthropometric data, so if there were to be changes in behaviour & subsequent readings, they’re going to be able to spot it and report it pretty quickly.

Now on the other side of this, if someone is incredibly turbulent with their nutrition, often partakes in large periods of fasting (be it intentional or not), lacks an understanding of what it means to be properly fuelled for an activity, or is perhaps looking to gain bodyweight following a period of inactivity/illness/atrophy- then my god, i’d have a really hard time coming up with a convincing argument that showcases this individual as a candidate for this drug.

A conclusion that probably doesn’t influence your opinion in any capacity

I bet you’re furious I haven’t come out here and ripped apart this drug or called your best mate a lazy twat because they’re choosing to use it. Life is about context and nuance. Your ability to approach something with nothing more than a desire to understand and learn, is paramount. Consider why someone may have opted for the use of something like this. Is there a lack of education surrounding it? Are they in a position where they deem themselves as ‘the ideal candidate’ that I've touched on? Did they get it ‘dead cheap from their hairdresser Becky who’s also doing teeth whitening for just £39 for the rest of November’? Honestly there are always going to be arguments for and against the use of any supplement or drug, but formulate your own opinion based on the scientific literature we have available, the experts in this field and most importantly, this sensational article.

I’m always keen to hear anyone’s thoughts on this and to further the discussion so please, just reach out if something in here has touched a nerve or if you have some more questions off the back of it!