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The Peptide Podcast

The Peptide Podcast

By: The Peptide Queen
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 The Peptide Podcast makes health and wellness decisions SIMPLE, FAST, and FUN. In less than 15 minutes each weekday, you'll get accurate, unbiased updates on peptides—from disease prevention and performance health to anti-aging and more. Hosted by The Peptide Queen, a clinical pharmacist with more than 15 years of experience, the show cuts through internet confusion to give you clear, reliable information so you can choose what's best for you.This website and its content are copyright of The Peptide Podcast - All rights reserved. Any redistribution or reproduction of part or all of the contents in any form is prohibited. Alternative & Complementary Medicine Exercise & Fitness Fitness, Diet & Nutrition Hygiene & Healthy Living
Episodes
  • ATX-304: Exercise In A Bottle

    ATX-304: Exercise In A Bottle
    Nov 6 2025
    Welcome to The Peptide Podcast. If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. https://pepties.com/partners/ Before we jump in, I want to quickly address a few comments I have received about the content here. Normally, I wouldn't spend time on something like this, but just for clarity — I have over nine years of formal education, including a Doctorate in Pharmacy, and sixteen years of clinical experience. That includes serving as an adjunct professor at a U.S. pharmacy school and working in oncology and inflammatory disease at a teaching hospital. And yes — for now, you just hear my voice, but that may change. I do plan to incorporate video in the future; I've simply held off because it takes significantly more time to produce, and my priority has been getting the education out to you consistently. Remember, the content is free and meant for education. If it's not for you, that's completely fine — you don't have to listen. It takes a lot of time and energy to put this together, and tuning in is entirely your choice. For my other listeners, thank you for your support and gratitude over the past few years. Now, today we're diving into a compound ATX‑304. It's often referred to as "exercise in a pill". And after we go through the science together you'll see why. We'll cover the back‑story, how it works, how it differs from typical mitochondrial supplements, animal and human data so far, who this may and may not be for — and importantly, what to watch out for. The Backstory & Why It's Getting Attention ATX-304, was first developed in Sweden by Betagenon AB as a small-molecule AMPK activator designed to mimic the metabolic benefits of exercise and caloric restriction — with the goal of improving obesity, insulin resistance, and overall metabolic health. Early preclinical work in obese and diabetic mice showed impressive results, including better glucose uptake, enhanced fat-burning, improved insulin sensitivity, and even cardiovascular benefits. Human data followed in 2016–2017, where people with type 2 diabetes already on metformin took ATX-304 for about 28 days. Those studies showed reductions in fasting and plasma glucose, improved insulin resistance, and strong safety and tolerability. Today, Betagenon has evolved into Amplifier Therapeutics, and ATX-304 is now in Phase 2 development for metabolic, cardiovascular, and liver-related conditions, with ongoing work to refine oral delivery and broaden its potential uses. What exactly does AMPK do? Think of AMPK as a fuel gauge for your cells. When your cells are running low on energy (like when you haven't eaten, exercised, or your cells are stressed), AMPK turns on. When it's on, it tells the cell to stop storing energy (less fat and cholesterol production), start using energy (burn sugar and fat for fuel), and clean up damaged parts (autophagy, or cellular housekeeping). Basically, AMPK flips the switch from "energy saving" mode to "energy spending" mode, similar to how your body behaves during exercise or fasting. If AMPK is off or underactive, your cells tend to store energy instead of using it, which contributes to weight gain, insulin resistance, and low metabolic activity. So, activating AMPK — like with ATX‑304 — is like giving your body a nudge to burn energy, improve metabolism, and clean up the cells, even without intense exercise. And beyond just turning on AMPK, ATX‑304 also acts as a mild mitochondrial activator, meaning it helps the cell's "power plants" (mitochondria) run more optimally, increasing energy expenditure. Because of this mechanism, ATX‑304 is sometimes called an "exercise mimetic." Even though it's not a substitute for movement, it triggers many of the same downstream pathways. How It Differs From Mitochondrial "Supplements" There are many supplements out there that claim "boost mitochondria" (e.g., PQQ, CoQ10, NAD precursors). These may support mitochondrial health or function, but typically they don't change the body's energy‑balance set‑point or shift you into a state of enhanced energy usage. ATX‑304, however, directly activates AMPK (the master switch) and supports mitochondrial output — so you get signaling plus hardware improvement. This dual action is what sets ATX‑304 apart. Also: many mitochondrial supplements lack robust human metabolic‑dysfunction data; ATX‑304 has animal + early human trial data. What About Safety? In human trials (~28 days, T2D patients on metformin) ATX‑304 was safe, well tolerated, lowered fasting plasma glucose and insulin resistance. But because it's still early stage, long‑term safety and outcomes (fat‑loss, muscle preservation beyond short term, cardiovascular endpoints) are not fully proven yet. One of the most exciting things about ATX‑304 is that it encourages the body to burn fat while sparing lean ...
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    8 mins
  • Finding the Right Fit: Semaglutide, Tirzepatide, or Retatrutide

    Finding the Right Fit: Semaglutide, Tirzepatide, or Retatrutide
    Oct 30 2025
    Today, we're tackling a question that comes up often in peptide, weight loss, and nutrition clinics: why does one person see great results with semaglutide, while another responds better to tirzepatide—or even retatrutide? If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. https://pepties.com/partners/ All three peptides target the incretin system, but they act in slightly different ways—and those differences can dramatically affect outcomes. Let's start with the basics. Semaglutide is a GLP-1 (glucagon-like peptide-1) receptor agonist. It mimics the gut hormone GLP-1, which increases insulin when blood sugar is high (to help lower blood sugar), suppresses glucagon (which also decreases blood sugar), and slows gastric emptying. It also enhances satiety—so you feel full longer and eat less. Tirzepatide is a dual agonist, acting on both GLP-1 and GIP receptors. GIP—glucose-dependent insulinotropic polypeptide—also helps with insulin secretion to lower blood sugar, increases fat metabolism, and may reduce some of the GI side effects seen with GLP-1 alone. Retatrutide, the newest in the lineup, is a triple agonist that targets GLP-1, GIP, and glucagon receptors. Retatrutide lightly activates the glucagon receptor while strongly activating GLP-1 and GIP receptors, which help regulate blood sugar and boost insulin secretion. This keeps blood sugar stable—or even improves it. Beyond blood sugar, glucagon also ramps up metabolism and calorie burning. By gently engaging glucagon receptors, retatrutide can increase energy expenditure and support fat loss without triggering large blood sugar spikes. So how do you decide which one might work best? Let's walk through common clinical situations. Patients with Hypothyroidism Let's talk about hypothyroidism. People with hypothyroidism often have slower metabolism, making weight loss more difficult even with a balanced diet. Low thyroid hormone levels slow calorie burning and energy use, so weight gain can occur more easily. For these patients, semaglutide is a reliable starting point—it helps regulate appetite and caloric intake. If progress plateaus, tirzepatide or retatrutide may provide an edge by boosting energy expenditure and fat oxidation, essentially "jump-starting" a slower metabolism. Patients with PCOS (Polycystic Ovary Syndrome) What about patients with PCOS (polycystic ovary syndrome)? Insulin resistance is common in PCOS, often leading to higher androgen levels (e.g., testosterone) and symptoms like irregular periods, acne, and excess hair growth. Hormonal changes also affect appetite-regulating hormones, increasing hunger and cravings. Both GLP-1 and dual agonists have proven effective in managing metabolic and reproductive aspects of PCOS. Typically, we start with semaglutide to improve weight, insulin sensitivity, androgen levels, and menstrual regularity. After a few months, if weight loss plateaus or cravings remain high, we may switch to tirzepatide. The added GIP activity enhances fat metabolism, insulin control, and may further support hormone regulation and ovulation. The key is starting with what's well-studied and tolerated, then stepping up if additional metabolic or reproductive support is needed. Type 2 Diabetes (T2DM) The next medical condition I'd like to talk about is type 2 diabetes (T2DM). Weight gain in T2DM often stems from insulin resistance. Cells don't respond effectively to insulin, prompting the pancreas to relelase more. High insulin levels encourage fat storage, particularly around the abdomen, while elevated blood sugar can increase hunger and cravings. Some diabetes medications, like insulin or sulfonylureas (e.g., glipizide or glyburide), can also contribute to weight gain. All three drugs lower blood sugar and promote weight loss, but tirzepatide currently shows the strongest combined A1c reduction (average blood sugar over the past 2 to 3 months) and weight loss. GIP and GLP-1 work together to enhance insulin response more effectively than GLP-1 alone. Retatrutide is in phase 3 trials, with potential FDA approval as early as 2027. Its glucagon receptor activity may offer additional glucose regulation and energy expenditure benefits. Patients with >15% Weight Loss Goals Okay, let's talk about weight loss goals and how this ties into the decision process for choosing a weight loss medication. For those patients looking to lose more than 15% of their total body weight, tirzepatide or retatrutide are likely to deliver greater results. Clinical data show semaglutide can achieve up to 15% total weight loss while tirzepatide can achieve up to 22% and retatrutide up to 24%. That said, semaglutide remains a highly effective option for weight loss. However, if progress begins to plateau, transitioning to a dual or triple agonist may help restart weight loss and push past that plateau. ...
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    13 mins
  • GLP-1's & Addiction

    GLP-1's & Addiction
    Oct 26 2025
    Today we're talking about peptides being researched for addiction. We'll unpack the science behind the incretin system, how those pathways tie into reward and substance use, and focus in on the newest triple‐agonist retatrutide. We'll also look at early evidence for alcohol, tobacco and other substance-use disorders when using certain peptide therapies. If you want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going. https://pepties.com/partners/ What are GLP-1, GIP and the "dual/triple" agonists? First, let's review some biology to ground the discussion. GLP-1 (glucagon‐like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are incretin hormones. Incretins are gut hormones that help with digestion and blood sugar control. They're released by the gut in response to food. GLP-1 raises insulin levels after you eat to help lower blood sugar, slows gastric emptying, and reduces appetite. It also reduces how much glucagon your body makes. This helps to lower your blood sugar. Medications like semaglutide and dulaglutide work by mimicking GLP-1 and are often referred to as "GLP-1 agonists". GIP has somewhat overlapping but distinct roles from GLP-1. It too, influences insulin secretion, but it also helps with fat metabolism. In a nut shell, GIP helps fat cells respond more efficiently to insulin so they release stored fat to be used as energy when your body needs it. This process helps your metabolism shift from just storing energy to burning fat for fuel. Medications like tirzepatide work by mimicking both GLP-1 and GIP and are often referred to as "dual" agonists. When GIP and GLP-1 are activated together — like in tirzepatide — they work as a team: GLP-1 helps control appetite and slow down digestion. GIP boosts how your body handles insulin and energy. Together, they help reduce hunger, improve metabolism, and burn fat more efficiently. Now here's where it gets a bit tricky. A newer medication that's still in development, retatrutide, works on three hormone pathways: GLP-1, GIP, and glucagon receptors. It's called a "triple agonist", and even though it activates the glucagon receptor, it doesn't cause high blood sugar like you might expect. It's about balance. In type 2 diabetes and obesity, the body's hormone signals are out of balance. Retatrutide gently activates the glucagon receptor, but at the same time it strongly activates GLP-1 and GIP receptors — which still help control blood sugar and increase insulin. So blood sugar stays stable or even improves overall. Glucagon doesn't just affect blood sugar — it also increases metabolism and helps the body burn fat and calories. By slightly stimulating glucagon receptors, retatrutide can boost energy use and promote fat loss without causing big spikes in blood sugar. As a result, you get the blood sugar control of GLP-1 and GIP, plus the fat-burning benefits of glucagon activation — leading to even greater weight loss and metabolic improvement. Right now, retatrutide is in phase 3 clinical trials, which are the final stage of testing before approval. These studies are expected to finish in early 2026, and if results look good, the FDA could approve retatrutide as early as 2027. Addiction Why is this relevant for addiction? Because the gut-brain axis, reward circuitry, and the pathways that regulate "wanting/consuming" food overlap with those involved in substance use. Appetite, reward, and craving may share neural substrates (dopamine, GABA, mesolimbic system) and so a drug that reduces drive to eat might also modulate drive to drink, smoke or use other substances. The link between GLP-1/related drugs and substance use disorders Let's now dive into what the research says about GLP-1 receptor agonists (and related medications) in the context of alcohol, tobacco, and other substances. Let's start with what we know from animal research. In pre-clinical studies, scientists have found that GLP-1 receptor agonists seem to change how animals respond to addictive substances. A systematic review showed that in rodents, treatment with GLP-1 drugs reduced the behavioral effects of alcohol, nicotine, amphetamine, and cocaine. For example, one GLP-1 drug called exendin-4 reduced alcohol-related behaviors in rodents. And even more recently, a study in both male and female rats showed that giving semaglutide, tirzepatide, or even retatrutide, reduced alcohol discrimination, meaning the rats didn't experience the same "feeling" from alcohol as before. This means that the "interoceptive stimulus effects" or the internal sensations — how alcohol feels inside the body, changed. This is really important because this is what often drives people to drink or relapse. So, if these medications can blunt those internal cues, it suggests they might disrupt the rewarding effects of alcohol that help maintain ...
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    7 mins
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