Shownotes
Nutrition Nugget! Bite-sized bonus episodes offer tips, tricks and approachable science. This week, Jenn is talking about Retatrutide, the third-generation injectable making waves as the most powerful weight-loss drug studied yet. It targets three hormone pathways at once instead of just one or two, and early trial participants have lost staggering amounts of weight, some over 30 percent of their body weight. But is more always better? Jenn breaks down how this triple mechanism works in the body, what the research shows so far, and why it might finally help the roughly 10 percent of people who never responded to earlier GLP-1s. Still, she has been raising the same concerns since Ozempic first came onto the scene, and this new drug is no exception. Is Retatrutide the breakthrough the weight loss world has been waiting for, or just a stronger version of the same unanswered questions? Tune in to hear Jenn's full take. Like what you're hearing? Be sure to check out the full-length episodes of new releases every Wednesday. Have an idea for a nutrition nugget? Submit it here: https://asaladwithasideoffries.com/index.php/contact/
RESOURCES:
Become a Happy Healthy Hub Member
A Salad With A Side Of Fries Merch
A Salad With a Side of Fries Instagram
Retatrutide—A Game Changer in Obesity Pharmacotherapy - PMC
International Journal of Molecular Sciences
Hyperglycemia vs. Hypoglycemia: Differences in Causes and Symptoms - GoodRx
Glucagon Control on Food Intake and Energy Balance - PMC
What Is Osteoarthritis? Causes, Symptoms, and Treatments - GoodRx
Potential Retatrutide Benefits You Should Know About - GoodRx
11 GLP-1 Side Effects You Should Know About - GoodRx
Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial | New England Journal of
Peptides for Weight Loss: What They Are and How They Work - GoodRx
Jenn Trepeck, Nutrition Nugget, Salad With A Side Of Fries, Health Tips, Wellness Tips, Retatrutide, Glp 1, Gip, Glucagon, Weight Loss, Ozempic, Wegovy, Mounjaro, Zepbound, Tirzepatide, Semaglutide, Insulin Sensitivity, Gastric Emptying, Appetite Suppression, Blood Sugar Control, A1c, Glycated Hemoglobin, Liver Steatosis, Fatty Liver Disease, Diabetic Kidney Disease, Type 2 Diabetes, Metabolic Dysfunction, Cardiovascular Risk, Osteoarthritis, Bone Density, Muscle Loss, Body Composition, Clinical Trials, Phase Three Trials, Injectable Medication, Weight Loss Drug, Pharmaceutical Intervention, Hunger Hormone, Satiety, Nausea, Constipation, Gastrointestinal Side Effects, Compounding Pharmacy, Counterfeit Medication, Obesity Treatment, Incretin Hormone, Retatrutide Weight Loss Results, Third Generation Glp 1 Medication
Transcripts
So this is the newest GLP [00:00:30] therapy. It's fitting for us to talk about it this week because our full [00:00:35] length episode this week was all about year four of salad with a cytofries, part of our [00:00:40] celebration of seven years of this podcast. Anyway, year four was the [00:00:45] first mention of GLP-1 pharmaceuticals. I did a nutrition nugget [00:00:50] on Ozempic in October of 2022.
Today, [:GIP, which stands for glucose-dependent [00:01:20] insulinotropic polypeptide. Say that 10 times fast. [00:01:25] GLP-1, which stands for Glucagon-like Peptide-1, as we've discussed [00:01:30] before, and glucagon. So let's walk through each one. So GIP, [00:01:35] glucose-dependent insulinotropic polypeptide. It's [00:01:40] excreted from intestinal K cells, which are hormone producing [00:01:45] cells in the lining in the small intestine.
GIP is a protein, mostly [:So what we see is that GIP stimulates glycogen [00:02:20] secretion, reduces appetite by having a negative impact on gastric emptying, [00:02:25] and by enabling insulin release from the pancreas acting together with [00:02:30] GLP-1. So GIP also impacts fat storage, the [00:02:35] formation of new fat cells, because smaller fat cells are better [00:02:40] for insulin sensitivity.
elps us use new food as fuel [:The second mechanism is GLP-1, that [00:03:10] glucagon-like peptide-1 that we've all sort of become familiar with, it seems like [00:03:15] these days. So as a brief reminder, GLP-1 is an incretin hormone [00:03:20] that is predominantly secreted from the intestinal tract, mainly as a response to [00:03:25] meals. It predominantly acts by activating a receptor that induces [00:03:30] stimulation of insulin release, decreases glucagon secretion, [00:03:35] reduces food intake, and delays gastric emptying by affecting gastric and [00:03:40] intestinal motility.
tells your [:So there are also GLP-1 receptors in reward-related [00:04:20] regions of the brain, like the hypothalamus, the amygdala, and [00:04:25] the brainstem, amongst some others. GLP-1 activation is also shown to [00:04:30] reduce inflammation by reducing macrophage activity. Its effects on [00:04:35] satiety and food intake are found in healthy individuals as well as [00:04:40] in obese based on BMI and diabetic patients.
All [:And in [00:05:10] combination with GIP and GLP-1, that's not an issue. [00:05:15] And the third one, glucagon. So this is a hormone that tells your liver to [00:05:20] make new sugar, and that's not an issue in combination with [00:05:25] GIP and GLP-1. And we can look to glucagon for its other [00:05:30] activities, which are speeding up metabolism and helping the body break [00:05:35] down fat cells for energy.
lucagon was discovered in the:Glucagon also reduces [00:06:05] GI motility. So again, we have that slower gastric emptying, slower [00:06:10] elimination, and this added metabolism boost can add [00:06:15] to and compliment what GIP and GLP-1 do. [00:06:20] So that's why the three in combination and retatrutide seem to [00:06:25] provide significant weight loss. So let's kind of sum this up.
[:So first generation [00:06:55] was semaglutides or semaglutides like Wegovy and Ozempic. [00:07:00] They acted on GLP-1 alone. The second generation of [00:07:05] GLP-1s had GLP-1 plus GIP. That's what we [00:07:10] find in tirzepatides like Zepbound and Mounjaro. Now, [00:07:15] retotrutide is the third generation with three receptor [00:07:20] targets. So the question is, what does this all mean for impact?
[:Next are phase three trials, which some have [00:07:55] started, some are ongoing, some have yet to begin. All of this to say, [00:08:00] it is not yet fully approved, it is investigational. And [00:08:05] we also don't have long-term safety and efficacy data [00:08:10] in diverse populations. We'll come back to that when we talk about some of the phase three trials, but let's [00:08:15] look at what the studies are showing us.
it's showing dose-dependent [:On the phase one and [00:08:40] phase two human trials, the ones that I saw were relatively small studies, [00:08:45] so I would love to see more and bigger sample sizes, which [00:08:50] should be coming in these phase three trials. What researchers found so far is that [00:08:55] retotrutide led to about a 28 or 30% weight loss. [00:09:00] On average, participants in a retotrutide clinical study who [00:09:05] received the study drug rather than a placebo lost an average of [00:09:10] 70.3 pounds over a year and a half, with more than [00:09:15] 45% of the participants losing more than 30% of their body weight.
Participants who [:We don't know what to [00:09:45] expect, not just in the first few weeks of using retotrutide, [00:09:50] but also in the longer term beyond a couple years. Now, there's another piece of [00:09:55] retotrutide that's interesting. So in some of the phase three trials, they're looking at some specific [00:10:00] populations of people. So there's a phase three trial with people who have osteoarthritis of [00:10:05] the knee who are also considered obese based on BMI.
Another is [:[00:10:40] So it's showing similar gastrointestinal side effects [00:10:45] as other GLP-1 medications like diarrhea, nausea, vomiting, [00:10:50] constipation tend to be the most common. I personally have seen more [00:10:55] dramatic impacts, especially sort of the snowball of [00:11:00] constipation, slower gastric emptying, and that in combination with some other food [00:11:05] choices can exacerbate some of these side effects.
f the biggest questions with [:In my own practice as a health and lifestyle coach, I am seeing [00:11:45] retotrutide impact the hunger and satiety for clients who did not [00:11:50] notice any difference really with the other GLP-1 medications. And with that said, I [00:11:55] still have the same concerns as with other GLP-1s. [00:12:00] I talked about this a lot in my op-ed episode from [00:12:05] earlier this year.
medications are [:[00:12:30] With the GLP-1s, we're seeing numbers in the medically preferred ranges in [00:12:35] blood work, and yet, I'm not sure we're really moving the needle on, [00:12:40] you know, really long-term outcomes because we have to take [00:12:45] into account muscle loss and bone loss and some of these other pieces. [00:12:50] So I will also say in my own practice, going back to that and just what I'm seeing with [00:12:55] people, I have clients who are on GLP-1 medications whose numbers are [00:13:00] all in range, and we're still seeing progressive impact [00:13:05] of type two diabetes and metabolic dysfunction in other parts of the [00:13:10] body.
e, they're still not looking [:Okay, off my soapbox for retotrutide. Remember, it is still [00:13:35] technically investigational. Phase three trials are expected to have much [00:13:40] larger sample sizes and hopefully they're looking at both shorter and longer periods [00:13:45] of time. It seems like it's probably on track for approval in [00:13:50] 2027. If it's approved, it'll be the first in this new class of [00:13:55] drugs and still likely to be administered as once weekly injection.
In the meantime, [:And now, you'll know about it when people start to talk about it in your [00:14:30] circles or you see it online. Well, as always, everyone, I am your host, [00:14:35] Jenn Trepeck. Connect with me on Instagram or all social media. I am @jenntrepeck, [00:14:40] J-E-N-N-T-R-E-P-E-C-K. This is your personal invitation to send me [00:14:45] a message if you'd like our website, asaladwithasideofries.com.
Pick your [:You'll go to [00:15:10] asaladwithasideofries.com/membership. This shows your support for this podcast, this community, and [00:15:15] above all, your health. On top of interview episodes in full video with behind the scenes [00:15:20] pieces, your twenty four seven Ask Me Anything on the community board, you'll get this week's recipe for [00:15:25] peach and pepper tacos.
Well, friends, that's it for [:Happy [00:15:50] [00:15:55] healthy.