Triple Agonists: The Next Big Thing in GLP-1 & Metabolic Medicine?

In this episode of Hormones and Hope, Dr. Chhaya Makhija breaks down one of the most rapidly evolving areas of modern medicine: GLP-1 receptor agonists.

With new medications, expanding FDA approvals, and growing conversations about weight loss, diabetes, longevity, and metabolic health, it can be difficult to separate evidence-based science from social media hype.

Dr. Makhija explains the differences between semaglutide, tirzepatide, and the highly anticipated triple agonist retatrutide while helping listeners understand what we know today—and what remains under investigation.

She also discusses why personalized care matters when prescribing GLP-1 medications, how these therapies may impact long-term health beyond weight loss, and why patients should be cautious about compounded or unapproved versions of emerging drugs.

Whether you're currently taking a GLP-1 medication, considering one, or simply curious about the future of metabolic medicine, this episode provides a practical, science-backed overview of where the field stands in 2026.

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Transcript

SPEAKER_00 0:00

Now, if you're tuning into this episode, I already know something about you. You're someone who genuinely cares about evidence-based medicine. Today's episode's answers are one of the most common questions that I've been receiving in the last few weeks from patients, family members, even other clinicians, audiences, DMs, at speaking events, and so on. And that question, especially this one, what do we actually know about GLP1 receptor Agnes right now? The science, the new developments, the rapid evolution, and where is this all going for your health? Welcome to Hormones and Hope, a podcast where we bridge science and wellness to help transform your health. I'm your host, Dr. Chaya Makija, or you can call me Dr. Chaya, a triple board certified endocrinologist and lifestyle medicine physician and founder of Unified Endocrine and Diabetes Care. Each week we dive into the powerful intersection of clinical medicine and real-life lifestyle strategies to help you feel stronger, live longer, and show up as your most vibrant self inside and out. So let's get empowered. Hello and welcome to another episode. This is your host, Dr. Makija. Now, if you're tuning into this episode, I already know something about you. You're someone who genuinely cares about evidence-based medicine. You're someone who cares about being updated on science. And more importantly, you're someone who's choosing your sources carefully. You're not just clicking on every headline, you're showing up for evidence-based science and conversations with both certified physicians and actual scientists who have worked in clinical trials, who are seeing and treating patients, and you trust real information, and I'm here to help you simplify it. I want to acknowledge that because in the world we are living in right now, this is not a small thing, that decision to seek legitimate expert-driven discussions to protect your health, is so genuinely appreciated. And I want to thank you genuinely. Now, let's get into today's topic. Today's episode's answers are one of the most common questions that I've been receiving in the last few weeks from patients, family members, even other clinicians, audiences, DMs, at speaking events, and so on. And that question, especially this one, what do we actually know about GLP1 receptor Agnes right now? The science, the new developments, the rapid evolution, and where is this all going for your health? Before I go anywhere, if you've not listened to my previous episodes on GLP 1 medications in terms of how to take it, what are the different kinds, side effects, the thyroid and GLP1 episode is also very, very informational. Go back to those first and then continue with this episode. For those who've already tuned in, I thank you and let's get into it. Now, the foundations are very important to know why we are sharing what we are sharing today. So GLP1 receptor agonist stands for glucagon-like peptide 1. It is a hormone that every one of us, all humans, naturally produce. It's in our gut, in our intestines. It is our own biology. The challenge is its half-life. By the time it appears in the bloodstream and creates its effect, it disappears again very rapidly. And we are talking about within two to four minutes. That's just not long enough for it to be therapeutically useful if you were using GLP1 as a medication. So did scientists do? Science did something very remarkable. It designed a longer acting version of the same molecule, a GLP1 receptor agonist, which is structured and engineered in such a way, and that's why these are called peptides, that it attaches to the same receptors that the natural GLP1 hormone does. But it stays active for a prolonged period for days, and that's why many of these medications are once a week injectable versus once-a-day pill. Now, the most well-known example of a GLP1 receptor agonist is semaglutide because we've had that since 2017 in the form of a Zempic, and then after that it got FDA approved as Vigovi for weight management. Semaglutide is just one hormone, one receptor target, and that's why it is one GLP1 receptor agonist. Now, let's talk about two, the dual agonist. The dual agonist is exactly what it sounds like: two hormones, two receptor targets. Number one is GLP1 receptor agonist, glucogon-like peptide, combined with another molecule, another hormone that is GIP, or glucose-dependent insulinotropic polypeptide. So two hormones, two receptors being activated simultaneously, and that's why dual agonist, and that is terzeptide, what you are aware of as manjaro for type 2 diabetes or zept bound for sleep apnea management as well as for weight management. Now, both of these, that is manjaro and zep bound in the form of terzepatide, same molecule, different FDA approved indications. Now, what that tells you is the difference. Right? Now, in general, when you look at clinical comparisons, because terzipatite is dual agonized to hormones, it does show a slightly higher percentage of weight reduction in clinical trials as compared to semaglutide. More receptor activity, more potency. But that is not necessary when you are customizing, personalizing treatment for our patients. That is clinical trial. In clinical medicine, in practical real world, we are just not looking at a number on the scale to figure out if this is going to be effective or this is going to be the prescription. We are working with you, the whole patient, right? Which medication do you tolerate? What are your previous histories of any hypersensitivity reactions? Which FDA approved medication would you need for that specific medical indication, right? Is it type 2 diabetes? Is it obesity? Is it sleep apnea? Is it fatty liver disease? And then comes a million-dollar question is what is your insurance actually going to cover? What is the formulary? Or during that conversation that we're having, it's not covered at all. And do you have to go to the route of self-pay prices for these medications? Now, these are all the discussions that are happening in uh the clinic in the exam room with the clinician and the patient. Again, I wanted to clarify these discussions, this education that is happening today is purely specifically for FDA-approved medications. Now, if you wanted to get a full uh breakdown of uh the FDA-approved indications, what kind of GLP1 receptor agonist? I have a free six-page GLP1 guide available. It's pretty robust to start with, and it's updated as of April 2026 because of the newer FDA-approved GLP1 receptor pills or oral options that is uh Vicovi and Fundio. The link is going to be in the show notes. You can download it, or you can just go to my Linktree, my social media handles. It's worth a resource having it for your friends, families, or even if you're a clinician, or if you are someone who's thinking about GLP1 receptor agonist. Now, we talked about semaglutide, trazipatide, one hormone, two hormones. Now, uh in the near future, we may have or we will have three hormones that is a triple agonist. You've heard about it everywhere in newspapers, New York Times, TikTok, and so many social media platforms and channels. It is everywhere in the metabolic health world. And I would want to give you the clarity and the real picture of where things actually stand in this specific realm of the class of medication that is the triple agonist, retatrotide. It activates three receptors instead of two GLP1, GIP, and the third one is glucagon. So three hormones, three receptor targets working simultaneously. Now, it is not out in the market as an FD-approved medication as of this recording, which is May, June 2026. Okay, we just have the data from the phase three uh trial, which means it is being it was conducted in humans and there were great robust results. And once these results are published, then they have specific protocols and steps to follow where they are submitted to FDA, uh food and drug administration. It's reviewed by panel, by experts, and then once all these uh reviews have been done and it's deemed to be safe and uh okay for FDA approval, then gradually it gets into the market, the insurance coverage and so on, and available as a prescription. So the clinical trial uh was called Triumph, and there are multiple one, two, three based on different indications that this medication is being studied that is retratride. The early results from um from clinical standpoint are pretty robust. Uh yes, they are exciting, but like I said, these are all clinical trial or relevant data. It's not available as a prescription at your physician's office. So, a very important point that you do not want to miss. If you are hearing from someone on social media or in your family gatherings or um your outings that they are on a triple agonist or they are on retatrotide and they're experiencing magical results, I want you to pause and ask a very important question. Where did the medication come from? Because what they're likely taking is either a compounded version or an outsourced version of that molecule and not studied for safety, uh, not reviewed for efficacy in humans and not been through any regulatory process. So when someone's taking such kind of medications or claiming to be on such medications and uh the results, question it because I am sharing with you the current data on an actual medication, and to get the right knowledge, this is also to help you avoid fear and anxiety, but also um have the reins of this knowledge that um your health, your body, should be uh treated in a very safe manner. You deserve to know what you're taking, what's being studied, um, what's the safety profile, what is the long-term data. It is not just an optional information. This is all fundamental when you're talking about health, right? Um any drug that is going into your system, you need to know about it and if it's legit, if it's FDA approved or not. Now the timeline. If um everything goes well and uh retatrotide, that is a triple agonist, uh, gets an FDA-approved stamp, uh, then uh we may have this medication available in 2027. We'll get there. You're not there yet. Trust the science, trust the process, and please be very careful what resources you're relying on, the information about GLP1 receptor agonist, what's going into your body. Okay. Now, beyond the triple agonist, the research landscape for GLP 1 receptor agonists right now is very, very remarkable. There are ongoing trials studying different types of GLP1 receptor agonists and different types of molecules for uh neosteoarthritis, for dementia, for Alzheimer's, uh also simultaneously other studies looking for cardiovascular outcomes. Many of them have been established, many of them going on, and also for fatty liver disease. We are in this era in 2026 watching a class of medications evolve in real time, from glucose control in type 2 diabetes to cardiovascular reduction to metabolic transformation and to potentially neuroprotective effects, knowing that anti-inflammatory effects do exist with this class of medication. The science is telling us that these receptors are present in tissues and in multiple areas of the body, and that activating them may give benefits that we are learning or we just started to understand. So, yes, the answer to the question in the title of this episode that is GLP1 receptor agonists are beginning to look like both medicine and a tool for longevity. Now, I have an episode with an expert, Dr. Ali, regarding longevity because you also want to understand longevity in the right manner for science. It's also reducing the risk of cancers, reducing the risk of your cardiovascular diseases, reducing the risk of metabolic diseases, which helps to improve our health span, our quality of life, less dependence on multiple medications and less complications equal to longevity. And the overlap is also the right nutrition, the right mindfulness, the right state of mind, the right exercise, strength training, your capacity of intense training and so on, right? So longevity is this big umbrella, and just one medication or one tool is not going to fix it or not going to help you obtain it, but it is a comprehensive use of these tools in the right manner with the right knowledge and assessing do I, as an individual, as a person need it, not just being influenced that if everybody needs it, I need it. Okay? So we are not working based on hype. We are actually getting the knowledge, understanding of GRP1 receptor agonist, understanding what is longevity medicine, understanding how to reduce the risk of chronic diseases, knowing the data, and follow along as I learn more, as I share the evidence-based data and keep breaking it down for you. Send me questions. I love these questions, email them, DM me, or wherever you meet me definitely, because these questions help me to build more answers for you. Empower myself, of course, with the knowledge, but that empowerment is just not limited to me. It's out there for all of you, my patients, and the community. So I really appreciate you supporting this mission. Now, if you're currently working with a clinician, whether it's through a telemedicine platform or otherwise, and your doses are being increased very rapidly, almost every month, that you're feeling fatigued, you have no appetite, you're feeling miserable, you're missing work, and you're intimidated to speak up. I want you to hear this clearly too. That's not good care. You deserve better. Go get a second opinion. I've been getting a lot of second opinions. Young individuals who are saying that I am with the telemedicine platform, I don't get to see the clinician, which is not a doctor, and I get a new prescription of a higher dose of GLP1 receptor agonist every time, and they're actually meeting the medical condition criteria. So those are all legit prescriptions, but the dose titration is not being personalized. So aggressive escalation on a fixed schedule without considering the patient's tolerability is not the right way to prescribe, treat a patient, or practice medicine with GLP1 receptor agonist. Your body composition is essential. What is happening to your lean body mass? You know, how are you feeling? What's happening to your appetite? Is it being suppressed? So who's going to assess your nutrition? If you're going to feel miserable, there is no use of reading a lot of data on nutrition. We need to fix that appetite, right? We need to readdress it, rebalance it, also look at your bowel movements, your hair loss, your water intake, and so on. There is this ongoing conversation needed. I am really emphasizing on this. Your labs, your discussion with the clinician one-on-one is going to be so very important and meaningful for the full metabolic picture and not just your weight. And that's going to bring you the long-term success. A clinician who can answer your questions, adjust your dose, have this patient-physician shared decision making rather than one-way channel. Now, you're not being difficult by asking better care. You're just advocating for your health. And I'm here to root you for that. And that's always the right thing to do. Because one size does not fit all. Injectable, oral, weekly, once daily, single agonist, dual agonist, and so much more coming. There is a lot in this field and it's exciting, but uh the foundations are important, your knowledge is important, those are non-negotiables for you. I appreciate you tuning into this episode. And before I let you go, a quick and important reminder. If you're listening to this episode on June 4th or June 5th, 2026, remember Dr. McKeeja's metabolic method, the masterclass M3 is happening right now. There is still time to join us. It's a free live five-day masterclass covering foundations of metabolic health, CGM, GLP1U, unnuances, your hormones, sleep, cortisol, nutrition, so much more, and question and answer every session with me, real conversations, but I'm not having any replays available for that. You can register at unified endocrine care.com forward slash contact or scroll down to find the M3 class registration in the show notes. Come join us and bring someone who really needs to hear this. If you're listening after June 5th, just stay connected. Thank you for tuning in. More episodes, more physician guests, more expert conversations are coming along the way. My goal is always the same: to leave you more empowered, more informed, and better equipped to take care of your health, you live in. I'm rooting for your health every single day. Until next time, this is Daka Chaya Makija, and you're listening to Hormones and Hope. Thanks for hanging out with me on Hormones and Hope. If you've loved this episode, do me a favor, hit subscribe, share it with someone you care about, and drop a review if you're feeling generous. Want more tools to support your hormones and health? Head over to unified endocrine care.com. We've got free guides, resources, and more waiting for you. Until next time, stay curious, stay kind to your body, and keep your hormones happy.