Retatrutide for weight loss, T2D, NASH ...

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Eddy Edson

Eddy Edson

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Relationship to Diabetes
Type 2
The drug pipeline is delivering a bunch of new weight loss med candidates, as showcased at the current ADA scientific sessions.

This includes GLP-1/GIP/Glucagon receptor tri-agonists, with EliLilly releasing results for Retatrutide's Phase 2 trial today. Average of 24% weight loss at 48 weeks without reaching plateau. Mild-to-moderate transient gastro side-effects.

In other words: meds have reached the point where they look like they're about as effective for obesity as bariatric surgery.

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Story in Nature: https://www.nature.com/articles/d41586-023-02092-9

Beyond Ozempic: brand-new obesity drugs will be cheaper and more effective​


Two new drugs for treating obesity are on course to become available in the next few years — and they offer advantages beyond those of the highly effective blockbuster drugs already on the market. The first, called orforglipron, is easier to use and to produce, and it will probably be cheaper than existing treatments. The second, retatrutide, has an unprecedented level of efficacy, and could raise the bar for pharmacological obesity treatment.
....
Whereas orforglipron could bring pharmacological weight management to a wider population, retatrutide could provide an unprecedented level of weight loss. At the highest dose used in the trial, participants lost an average of 24.2% of their body weight over 11 months of treatment. Currently approved drugs tend to yield around 15–20% weight loss over a similar time period. Retatrutide “will likely reset our expectations for what we consider an efficacious obesity drug”, says neurobiologist Amber Alhadeff at the Monell Chemical Senses Center in Philadelphia, Pennsylvania, who was not involved in either study.

What’s more, all participants in the retatrutide study who received higher doses lost at least 5% of their body weight. The currently approved drugs, by contrast, work in about 90% of the people who take them. “This is great, but when you’re a clinician seeing 60–80 patients per week, 10% of them will come back disappointed,” says obesity-medicine specialist Beverly Tchang at Weill Cornell Medicine in New York City. Retatrutide interacts with three receptors that determine appetite, which is probably why it’s so effective, she adds. Wegovy interacts with one receptor, and Mounjaro interacts with two.
 
Yoni Freedhoff has a good article in TIME on the moralising & other common inept negative talking-points about these kinds of meds:

https://twitter.com/x/status/1674093806688280580
https://time.com/6290294/weight-loss-drugs-ozempic-demonization-essay/

The one I see most commonly:

9. Lifestyle alone is sufficient.​

That is true for a small percentage of people. But for the rest, sustained significant weight loss through lifestyle alone requires wide ranging privilege and even then, there are dozens if not hundreds of factors affecting our weights beyond our direct control – from genetics, to medical challenges, to our social determinants of health. Moreover, the vast majority of chronic non-communicable diseases are modifiable by way of lifestyle, yet it’s only with obesity where this false dichotomy about behavior as the only solution is pushed hard and therefore that it’s a failure to offer medications.


There is no magic diet which works for everybody; all of them (low carb, low fat, whatever) work for only a small percentage of lucky people. And it is not the case that for every person there is some individual magic diet.

Health Nerd had a piece yesterday with a light-touch summary of the evidence: https://gidmk.medium.com/there-is-no-best-way-to-lose-weight-243a8d64084e
 
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Whilst anything that helps cannot be ignored, it concerns me how these things are viewed "in the wild", by both patients and professionals.

I recently attended a focus group, for an up-coming research piece, looking at injectables, in the Ozempic grouping. The researcher was very excited about their potential, but expressed it as removing glucose equivalent to 2 cans of coke per day.

Now, know people as we do, there will be some who just interpret that as them being able to continue to consume coke, because their meds will take care of it.

I have prepared my feedback for the meeting, but will submit it after reading a part of the presentations slide, which I have requested. Unfortunately, I had to dip out of the meeting early due to an overlapping diary clash. They may have covered the communications side of things in the slides I missed, so want to be fair.

Like so many things in life, the communication of the proposed treatment plan. The more of these drugs I see appearing the worse I fear our T2 diabetes problems will become.

(To be clear, that doesn't mean I want them banned, but used with extreme caution.)
 
AndBreathe said:
Whilst anything that helps cannot be ignored, it concerns me how these things are viewed "in the wild", by both patients and professionals.

I recently attended a focus group, for an up-coming research piece, looking at injectables, in the Ozempic grouping. The researcher was very excited about their potential, but expressed it as removing glucose equivalent to 2 cans of coke per day.

Now, know people as we do, there will be some who just interpret that as them being able to continue to consume coke, because their meds will take care of it.

I have prepared my feedback for the meeting, but will submit it after reading a part of the presentations slide, which I have requested. Unfortunately, I had to dip out of the meeting early due to an overlapping diary clash. They may have covered the communications side of things in the slides I missed, so want to be fair.

Like so many things in life, the communication of the proposed treatment plan. The more of these drugs I see appearing the worse I fear our T2 diabetes problems will become.

(To be clear, that doesn't mean I want them banned, but used with extreme caution.)
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Yes, it is vital to ensure that we are not conducing to the moral turpitude of the lower orders.
 
Eddy Edson said:
Yes, it is vital to ensure that we are not conducing to the moral turpitude of the lower orders.
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I grudge nobody anything that improves their health and wellbeing, but alone, all these have the potential of doing is enabling further "unhealthy" behaviours in those not engaged with what I would see as their end of the deal.

If/when approved for widespread use, filtering in/out suitable candidates could become a (very costly) nightmare.
 
AndBreathe said:
I grudge nobody anything that improves their health and wellbeing, but alone, all these have the potential of doing is enabling further "unhealthy" behaviours in those not engaged with what I would see as their end of the deal.

If/when approved for widespread use, filtering in/out suitable candidates could become a (very costly) nightmare.
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As Yoni says:

10. Their use will cause eating disorders.​

Which do you think is more likely to lead to disordered eating? Highly restrictive dieting that leaves a person battling hunger, cutting out their favourite foods or entire food groups, and involves a constant mental battle replete with perseverant and maladaptive thinking around one of life’s seminal pleasures which society claims should be doable if you just want it badly enough, or a medication that decreases your hunger, your cravings, and makes you feel full faster?
 
We live in a world where people want silver bullet solutions. The more they are told they exist and are available, the more they want them.
I am not saying there isn't a place for these medications, but I think there is a concern with making them appear to be that silver bullet.
 
rebrascora said:
We live in a world where people want silver bullet solutions. The more they are told they exist and are available, the more they want them.
I am not saying there isn't a place for these medications, but I think there is a concern with making them appear to be that silver bullet.
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You made my point so much better than I did.
 
My friend got sucked into this over a year ago when they became available privately. She read all the hype about them. Her GP would not prescribe because she was not sufficiently overweight to qualify for them, she went online and lied about her weight to get them and paid money she could ill afford, but wanted the quick fix. Then she frightened herself with some scary side effects and stopped taking them, so her money was wasted anyway. Ultimately they did not help her mentally or weight wise and financially she was out of pocket when she could have spent that money on more nutritious food.... of course she wouldn't though, because she wants the quick, easy fix.
 
Eddy Edson said:
As Yoni says:

10. Their use will cause eating disorders.​

Which do you think is more likely to lead to disordered eating? Highly restrictive dieting that leaves a person battling hunger, cutting out their favourite foods or entire food groups, and involves a constant mental battle replete with perseverant and maladaptive thinking around one of life’s seminal pleasures which society claims should be doable if you just want it badly enough, or a medication that decreases your hunger, your cravings, and makes you feel full faster?
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Fair points, but for those with either a current history of or a strong predisposition to disordered eating (and there is a lot of it about), feeling fuller sooner need not be a barrier, if having a chunk of digestive track removed in bariatric surgery, then subsequently not losing or regaining lost weight is anything to go by, folks with seriously disordered eating/thinking will just plough on.
I find it a great worry that we are storing up a problem we (as in the NHS) don't currently address. Will just just remain in that situation, except we (the public purse) will be having a ginagerous drugs bill to run alongside it.
 
rebrascora said:
My friend got sucked into this over a year ago when they became available privately. She read all the hype about them. Her GP would not prescribe because she was not sufficiently overweight to qualify for them, she went online and lied about her weight to get them and paid money she could ill afford, but wanted the quick fix. Then she frightened herself with some scary side effects and stopped taking them, so her money was wasted anyway. Ultimately they did not help her mentally or weight wise and financially she was out of pocket when she could have spent that money on more nutritious food.... of course she wouldn't though, because she wants the quick, easy fix.
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Diet (as in ways of eating) is at the core of so much in out lives.
 
I had/have an eating disorder and mental health problems, so I know how challenging it is, but for me going low carb helps me manage it far better than I believe it would be to continue poisoning my body with the junk I was eating, plus taking medication which also poisons the body to a greater or hopefully lesser extent (hence side effects), in order to allow me to continue eating that junk. To my mind, this isn't the answer and I think people will likely pay for it in some way in the long run and possibly be no better off, maybe worse.
 
rebrascora said:
in order to allow me to continue eating that junk
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This is just absolutely not what these drugs are for, and it is not what actually happens. It might be useful to find out more about them.
 
Eddy Edson said:
This is just absolutely not what these drugs are for, and it is not what actually happens. It might be useful to find out more about them.
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Yes, and the problem with the existing methods for dieting/lifestyle changes are that we have really, really, good evidence that they just don't work that well. I mean in principle they do, but in reality people commonly fail to lose weight.

Bariatric surgery works, but it would be really good to have some alternatives.

(Obviously changing society, enabling everyone to afford to buy fresh ingredients and to have the time to prepare them, etc., would be really good for lots of reasons, but sadly it's not going to happen.)
 
Eddy Edson said:
This is just absolutely not what these drugs are for, and it is not what actually happens. It might be useful to find out more about them.
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I think you underestimate the guile of some individual's living with disordered eating. Few talk about it, whilst it is active, and it is generally a secretive activity, so I doubt many doctors get to know about it until some sort of a crisis is hit.

People get creative about all sorts of things with their GPs, whether how many units of alcohol they drink a week, cigarettes then smoke daily, or indeed what they eat. An opportunity for a potential silver bullet? No brainer - for some.
 
I have read and absorbed the above discussion, I am a disordered eater.
I start a " new "diet every single day.
My head knows I must cut carbs and stop eating candy, I haven't managed to do this since a few years ago.
Why do I treat my body so badly, I eat freshly prepped and cooked meals when I feel well but most days I eat cereal and sandwiches with a few sweets in-between.
I hate myself every time I eat unhealthy food but I haven't yet managed to stop doing it. I am at my absolute biggest now, yuk !
My weight has doubled. I feel nauseous eating vegetables do not eat meat and am allergic to eggs.
I would like very much to try the injections but will not be prescribed them due to having thyroid disease.
Perhaps surgery is my only hope.
 
ell said:
I have read and absorbed the above discussion, I am a disordered eater.
I start a " new "diet every single day.
My head knows I must cut carbs and stop eating candy, I haven't managed to do this since a few years ago.
Why do I treat my body so badly, I eat freshly prepped and cooked meals when I feel well but most days I eat cereal and sandwiches with a few sweets in-between.
I hate myself every time I eat unhealthy food but I haven't yet managed to stop doing it. I am at my absolute biggest now, yuk !
My weight has doubled. I feel nauseous eating vegetables do not eat meat and am allergic to eggs.
I would like very much to try the injections but will not be prescribed them due to having thyroid disease.
Perhaps surgery is my only hope.
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Welcome to the forum @ell

And thanks for candidly sharing your experience with us.

Hope that one of the newer drugs comes along that fits with your thyroid condition, and that you are able to find ways to be kind to yourself while you explore the option of surgery.
 
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