Nutrition Nugget: Retatrutide

0:00Welcome to Salad with a Side of Fries. I'm your host, Jen Trepick, talking wellness and weight loss for real life. We're here to clear up the myths, misinformation, bad science and marketing to teach you how to eat and how to cheat. Are you ready? I'm having salad with a side of fries. This week we're talking about redditruthide. So this is the newest GLP therapy. It's fitting for us to talk about it this week because our full length episode this week was all about year four of Salad with a side of fries, part of our celebration of seven years of this podcast. Anyway, year four was the first mention of GLP1 pharmaceuticals. I did a nutrition nugget on ozempic in October of 2022. Today we're still here almost four years later and we have the next generation of these

1:00injectables. Actually, this is technically the third generation of these injectables. So let's look at what this one is, how it's different and what people are experiencing. So redditruthide has three mechanisms of action. GIP, which stands for glucose dependent insulinotropic polypeptide, say that 10 times fast, GLP1, which stands for glucagon-like peptide one as we've discussed before, and glucagon. So let's walk through each one. So GIP, glucose dependent insulinotropic polypeptide. It's excreted from intestinal casals, which are hormone producing cells in the lining of the small intestine. GIP is a protein mostly, what's called post-prandially secreted, which means after eating. It consists of 42 amino acids that require the breakdown of a 153 amino acid protein.

2:02Now GIP receptors exist as two different forms in multiple tissues, primarily in pancreatic beta cells, and secondarily at a post and nervous tissue. So what we see is that GIP stimulates glycogen secretion, reduces appetite by having a negative impact on gastric emptying, and by enabling insulin release from the pancreas acting together with GLP1. So GIP also impacts fat storage, the formation of new fat cells because smaller fat cells are better for insulin sensitivity, and then it also helps us use new food as fuel versus storing new food as fat. Additionally, GIP is shown to have a direct influence on bone, inducing what's called osteoblast activity. So this may be super helpful as we see bone loss as a significant side effect from a lot

3:02of these medications. So GIP is the first mechanism of action here. The second mechanism is GLP1, that glucagon-like peptide 1, that we've all sort of become familiar with, it seems like these days. So as a brief reminder, GLP1 is an incretion hormone that is predominantly secreted from the intestinal tract, mainly as a response to meals. It predominantly acts by activating a receptor that induces stimulation of insulin release, decreases glucagon secretion, reduces food intake, and delays gastric emptying by affecting gastric and intestinal motility. Like GIP, GLP1 tells your pancreas to release insulin after eating. GLP1 decreases the amount of glucose or sugar your liver makes, and helps you feel fuller longer. It also acts in areas of the brain that regulate appetite and impact food cravings. Now, similar to how we talked about how GIP has receptors around the body, GLP1 receptors

4:06can also be found in the pancreas, gastric mucosa, the kidney, lung, heart, skin, immune cells, and the brain. So there are also GLP1 receptors in reward-related regions of the brain, like the hypothalamus, the amygdala, and the brainstem, among some others. GLP1 activation is also shown to reduce inflammation by reducing macrophage activity. Its effects on satiety and food intake are found in healthy individuals, as well as in obese based on BMI and diabetic patients. All of this is likely why we may see some impact on other organs and in other parts of the body with GLP1 agnes. Okay, then the third mechanism of action in red atruthide is glucagon. So this is the hormone that tells your liver to make new sugar. It has long been part of the treatment for diabetes since it was discovered in like the 1920s.

5:09And in combination with GIP and GLP1, that's not an issue, and the third one glucagon. So this is a hormone that tells your liver to make new sugar. And that's not an issue in combination with GIP and GLP1. And we can look to glucagon for its other activities, which are speedy on metabolism and helping the body break down fat cells for energy. Now glucagon was discovered in the 1920s, so it has long been part of treatment for diabetes. Glucagon receptors are mainly found in the liver and in the kidneys. So less expression is also described. So there's potentially some receptor sites, although fewer of them in other tissues like the heart, the pancreas, adipose tissue, which is fat tissue, and the GI tract. Glucagon also reduces GI motility, so again, we have that slower gastric emptying, slower

6:09elimination. And this added metabolism boost can add to and complement what GIP and GLP1 do. So that's why the three in combination in redditure tide seem to provide significant weight loss. So let's kind of sum this up. Redditure tide acts on GLP1 receptors, GIP receptors, and glucagon receptors to suppress appetite, slow digestion, increase fat metabolism, increase insulin sensitivity, all of this to induce weight loss and improve glycemic control. In the context of existing pharmaceuticals, I think it's helpful to understand them in this way. So first generation was semagglutides or semagglutides, like wugovii and ozempic. They acted on GLP1 alone. The second generation of GLP1s had GLP1 plus GIP. That's what we find in terzepatides, like zepbound and manjaro.

7:14Now, redditure tide is the third generation with three receptor targets. So the question is, what does this all mean for impact? Okay. Animal studies demonstrate redditure tide does what we would expect. Delays gastric emptying reduces food intake, promotes weight loss. In terms of the studies, there were animal studies, then phase one and phase two clinical trials that corroborate or confirm the findings of the animal studies, which will walk through some of these findings in a second. Next are phase three trials, which some have started, some are ongoing, some have yet to begin. All of this to say it is not yet fully approved. It is investigational. And we also don't have long term safety and efficacy data in diverse populations. We'll come back to that when we talk about some of the phase three trials.

8:14But let's look at what the studies are showing us on the whole. It's showing dose dependent weight loss, reductions in glycated hemoglobin. So that's your A1C. That improvements in liver stiotosis and diabetic kidney disease. By the way, liver stiotosis, we talked about that in nutrition nugget on non-alcoholic fatty liver disease. So you can go back to that. On the phase one and phase two human trials, the ones that I saw were relatively small studies. So I would love to see more and bigger sample sizes, which should be coming in these phase three trials. What researchers found so far is that retitrutide led to about a 28 or 30 percent weight loss. On average, participants in a retitrutide clinical study who received the study drug rather than a placebo lost an average of 70.3 pounds over a year and a half with more than 45%

9:15of the participants losing more than 30% of their body weight. Those who had BMI's greater than 35 lost even more weight. So that was more around like 85 pounds or 30-ish percent of their body weight after about two years with that highest dose of about 12 milligrams. This seems to be more than any of the approved weight loss medications. I think the timeline here is worth keeping in mind. We don't know what to expect. Not just in the first few weeks of using retitrutide, but also in the longer term beyond a couple years. There's another piece of retitrutide that's interesting. So in some of the phase three trials, they're looking at some specific populations of people. So there's a phase three trial with people who have osteoarthritis of the knee, who are also considered obese based on BMI. Another is focused on people with type two diabetes and another on people with heart disease.

10:15So what we're seeing with retitrutide being studied for other health conditions is like type two diabetes, metabolic dysfunction, associated, stiato hepatitis. So that's mass or that non-alcoholic fatty liver disease like our other nutrition nugget. Chronic kidney disease I'll mention again, cardiovascular risk reduction, osteoarthritis of the knee and even chronic lower back pain. So it's showing similar gastrointestinal side effects as other GLP1 medications like diarrhea, nausea, vomiting, constipation tend to be the most common. I personally have seen more dramatic impacts, especially sort of the snowball of constipation, slower gastric emptying and that in combination with some other food choices can exacerbate some of these side effects. One of the biggest questions with retitrutide is if it will support people whose bodies didn't respond to the other pharmaceuticals.

11:17So right now it's about 10% of people who are not responding to other GLP1 meds, whether it's first generation or second generation. And so far it's looking like yes. So one physician said that 100% of the study volunteers who received 8 milligrams or more of retitrutide lost at least 5% of their body weight. In my own practice as a health and lifestyle coach, I am seeing retitrutide impact the hunger and satiety for clients who did not notice any difference really with the other GLP1 medications. And with that said, I still have the same concerns as with other GLP1s. I talked about this a lot in my op-ed episode from earlier this year. In that episode I said that I believe GLP1 medications are our generation statin drug. And the comparison is that it's a drug that a majority of people are on and yet not necessarily

12:18changing outcomes. So in the case of statin drugs, a vast majority of adults are on a statin drug and yet cardiovascular disease is still the number one cause of death. With the GLP1s, we're seeing numbers in the medically preferred ranges in blood work. And yet I'm not sure we're really moving the needle on really long term outcomes because we have to take into account muscle loss and bone loss and some of these other pieces. So I will also say in my own practice going back to that and just what I'm seeing with people, I have clients who are on GLP1 medications, whose numbers are all in range. And we're still seeing progressive impact of type 2 diabetes and metabolic dysfunction in other parts of the body. So with what we're seeing in the studies on reddit trutide, they're still not looking at body composition. They're still not looking at loss of muscle or bone, potentially with the way these other

13:22elements work. Maybe it can help on the bone front. I just think there's more that we need to look at and consider longer, longer term. Okay, off my soapbox for reddit trutide. Remember, it is still technically investigational. Phase 3 trials are expected to have much larger sample sizes and hopefully they're looking at both shorter and longer periods of time. It seems like it's probably on track for approval in 2027. If it's approved, it'll be the first in this new class of drugs and still likely to be administered as once weekly injection. In the meantime, be careful with people illegally selling counterfeit or gray market reddit trutide. Once it's approved, we may see compounding pharmacies offering the triple acting formulation to help with accessibility. This too carries considerations that you'll want to think about. All in though. That's the scoop on reddit trutide. The latest generation of pharmaceutical interventions.

14:26And now you'll know about it when people start to talk about it in your circles or you see it online. Well, as always, everyone, I am your host, Jen Trepik. And I'm an Instagrammer, all social media. I'm at Jen Trepik, J-E-N-N-T-R-E-P-E-C-K. This is your personal invitation to send me a message if you'd like our website, a salad with a side of fries dot com. Pick your platform. I want to hear from you your ideas, your takeaways, your questions. This is also the easiest way to learn more about working with me as your coach. And I truly want to say thank you for listening each week, each year and friend. If you are not already, join us in the happy healthy hub. You'll go to a salad with a side of fries dot com slash membership. This shows your support for this podcast, this community, and above all your health. On top of interview episodes in full video with behind the scenes pieces, your 24-7 ask me anything on the community board. You'll get this week's recipe for peach and pepper tacos.

15:28Well friends, that's it for today's episode of Salad with a Side of Fries. Congratulations for making yourself and your health a priority. Thanks so much for joining us. Be sure to click subscribe or follow on your favorite podcast platform. Share us with a friend and we'll be back next week. Please remember, you deserve it and you are worth it. Happy healthy.