Episode 245: Retatrutide Delivers Bariatric-Level Weight Loss: Breaking Down the TRIUMPH-1 Trial from ADA 2026

[00:00:00] Welcome back to the Back on Track: Achieving Healthy Weight Loss, where I help you get on track and stay on track with your weight loss journey. I'm your host, Dr. Alicia Shelly. So let's get started.

[00:00:27] Welcome back to the Back on Track Achieving Healthy Weight Loss podcast. I'm your host, Dr. Alicia Shelly. And today we are talking about one of the biggest stories to come out of the 86th Scientific Session of the American Diabetes Association, or the ADA.

[00:00:46] Now, throughout the year, there are multiple different conferences, one for obesity, one for diabetes, where they actually talk about the different medications that are coming out. And the researchers are able to share their projects and what they've been doing and the results. And so, earlier this month, the ADA, there were many different researchers that came out and talked about different trials, different studies and different medications.

[00:01:15] But the one we're talking about today is called the TRIUMPH-1 trial or study. This trial evaluated a medication called retitrutide. Now, I have spoken about retitrutide before, but now we have more and new data that we can use. And retitrutide, or RETA for short, is a once weekly injection that is showing impressive weight loss results that we've seen today from a medication.

[00:01:44] In fact, the amount of weight loss seen in this study is approaching what we traditionally expect from bariatric surgery. Participants lost on average 28.3% of their body weight over 80 weeks, so a little over a year, so over a year and a half. And some continued to lose even more weight even beyond that. So today, we are breaking everything down that was talked about in the ADA meeting.

[00:02:12] We're talking about what retitrutide is, why scientists are so excited about it, the major findings from the TRIUMPH-1 trial, and what this means for patients living with obesity, and when this medication may become available. So, let's jump in. So what is retitrutide? So most people are familiar with medications like Wegovy and Zeppon.

[00:02:36] Wagovi works primarily on the GLP-1 receptor, whereas Zepbound works primarily on the GLP-1 plus GIP receptors. Now, retitrutide takes this one step further. It is what is known as a triple hormone receptor agonist, meaning not only does it activate the GOP-1 receptor, also the GIP receptor, but then also glucagon receptors.

[00:03:03] So it targets three hormones in the body. So this third pathway, the glucagon receptor, is what really makes retitrutide unique. While we are familiar with GOP-1s and GIP and how they help reduce appetite and improve glucose regulation, glucagon actually can increase your energy expenditure and fat burning. So, or it just increases your metabolism. I remember I've had patients in the past who asked me like,

[00:03:33] is there anything that can increase my metabolism? And unfortunately, as we age, our metabolism just decreases. And what happens is, it's just aging, normal, it happens. But we have to do more, like more exercise in order to burn the same amount of calories as we did when we were maybe 10 years younger. So now, glucagon can help with increasing energy expenditure and fat burning.

[00:04:01] Also, researchers believe that this combination may explain why retitrutide is producing such dramatic weight loss results. Let's jump into the TRIUMPH-1 trial. So the TRIUMPH-1 trial was a phase three clinical trial involving adults with obesity or overweight. So either BMI of 30 or overweight, BMI of 27 plus a weight-related comorbidity. All the participants received were actually randomized to different arms.

[00:04:30] So some received different doses of retitrutide for 80 weeks. And there was a placebo arm, meaning that they received a sugar shot during that time. The highest dose studied was 12 milligrams weekly. And the primary endpoint or question that researchers wanted to answer was, how much weight can people lose with retitrutide? And the answer surprised even obesity medicine experts.

[00:04:57] Because at that 80 weeks of participants receiving 12 milligrams of retitrutide, they lost 28.3% of their body weight. That's an average reduction of approximately 70 pounds. So to put it in perspective, if someone weighs 250 pounds when they start this medication, 28.3% reduction will equal more than 70 pounds of weight loss.

[00:05:24] Even more impressive, they did an extension where they had, after they were done with the 80 weeks, they had people stay on their maxly tolerated dose of retitrutide. And if they were on the placebo, they switched to retitrutide. And for an additional 24 weeks, or basically at the end of 104 weeks, at the highest dose of retitrutide, there was an average weight loss of 30%.

[00:05:50] And some, which suggests that many participants are still losing weight after nearly two years of treatment. And the one thing I love about this study is that it looked beyond just averages and how much weight on average people lost. They actually looked to see, research has evaluated how many people achieved clinically meaningful weight loss milestones. For example, if you lose between 5 and 10% of your body weight,

[00:06:17] that can help improve your metabolic conditions like high blood pressure, pre-diabetes, insulin resistance. So it can actually help improve that. And in this trial, nearly almost everyone lost at least 5% of their body weight. More than 85% of the participants lost at least 15% of their body weight. And that was the starting average of WGOBI. And then more than one in four lost over 35%.

[00:06:44] So almost 25% of individuals lost at least over 35%. And these are numbers we simply have not seen with other medications. And many participants no longer met the criteria for obesity by the end of the study. So researchers reported that approximately two thirds achieved a BMI below 30. One third achieved a BMI below 25, which falls into the normal weight range.

[00:07:13] So think about it for a moment. A medication helped one in three participants move from obesity to a normal BMI category. That is a very powerful medication. And one of the most important messages that I share with my patients is that the goal isn't simply just weight loss or cosmetic. The goal is for better health. And the Triumph One trial showed improvements across multiple obesity related conditions. For example, obstructive sleep apnea.

[00:07:44] Participants experienced greater than 60% reduction in their apnea hypopnea index, which basically tells us how in a span of an hour, how many times the patients stop breathing or they shallow breathe per hour. And so rejection of 60% is pretty impressive. It also suggests a meaningful improvement in sleep apnea severity as well. And for patients who struggle with the CPAP machines or severe daytime fatigue,

[00:08:14] this can be life changing. Also, they looked at knee osteoarthritis. So researchers observed that more than 70, there was a 70% reduction in pain scores. This is huge. If you're somebody who has difficulties moving because of knee pain, back pain, things like that. I mean, to reduce your pain by 70%, that is pretty darn amazing. Also, many patients tell me that they want to lose weight,

[00:08:40] but not because the number of the scale, because their knees hurt, their hips hurt. They want to move again. This study suggests that reticuletide may help improve both weight and mobility. Also, another finding that caught my attention involved prediabetes. More than 95% of participants with prediabetes returned to a normal blood sugar level during the study. So imagine preventing diabetes even before it develops.

[00:09:08] And that's where obesity medicine is headed. Not just treating disease, but preventing it altogether. Researchers also reported improvements in your triglycerides, LDL, blood pressure. And these are the same risk factors that contribute to heart disease, stroke and metabolic dysfunction. So there's a lot of good, but what about those side effects? I'm sure you're thinking about it. And as exciting as these results are, it's important for us to discuss tolerability.

[00:09:38] And the most common side effects that we see here are gastrointestinal, so that nausea, vomiting, diarrhea, constipation, are the most common side effects at higher doses, especially between that 9 and 12 milligram dose. Researchers have also noted in increased reports of hypotension, especially among individuals taking blood pressure medication. And the reason being that you may not necessarily need the high dose of your blood pressure meds.

[00:10:04] And so sometimes you have to, with the help of the doctor, your provider, taper down on them. But if you haven't, then that can definitely lead to low blood pressure. Dr. Also, we look at how the discontinuation rates. So due to overall adverse reactions, for those taking retitrutide, it was 4 to 11 percent and 5 percent of those who received placebo.

[00:10:28] Also, when we look at the adverse reactions for GI side effects, the most common reasons were GI, of course, but the discontinuation rate was between 2.2 and 4.6 in retta and arms and 1.2 percent in the placebo arms. Also, there were some new adverse reactions of special interest such as dysethisia, which is skin burning. That occurred between 5 to 12.5 percent.

[00:10:54] Also, there's some injection site reactions that were also between that 5.5 and 12 percent as well. So this highlights something that I see in my clinic every day, that the most effective medication is not always the right medication for every patient. Because if you can't tolerate it, especially with all these side effects, then we need to try something else. And so treatments should always be individualized based on the person. So how does retitrutide compare to a set bound?

[00:11:23] Well, the one thing I will say is that we have not done any head-to-head trials, so it's kind of hard to compare. But if you look at the different studies, you can say that retitrutide can produce greater weight loss. However, there's no head-to-head trial or phase three data comparing the two drugs directly. What we do know is that set bound changed obesity treatment landscape. Retitrutide may then raise the bar even higher.

[00:11:50] And so tolerability may ultimately determine which patient benefits most from each medication. And then how much weight do you have? Do you need to lose 28.3 percent or can you lose 10 percent or 15 percent? So, you know, we're going to get to the point where we're tailoring this to each and everyone's individual-ness. When will retitrutide be available? Well, it's still considered investigational and has not received FDA approval yet.

[00:12:19] So just yesterday, I was watching a CBS nightly news segment and they were talking about doctors in the Los Angeles area who were selling retitrutide or retta for short. But, and they were advertising it on their website and everything, but retitrutide has not been FDA approved. So it cannot be utilized or be sold.

[00:12:41] So if you are seeing advertisements for retitrutide now, then I would definitely not buy anything from them because you don't know what you're getting. They could be selling you sugar water and you would not even know. So, you know, it's better to wait on the real thing. And it's anticipated that early 2027 this should be coming out. In conclusion, as an obesity medicine physician, what excites me the most is not the 28 percent weight loss.

[00:13:09] It's what the weight loss represents. So for years, patients have been told just eat less and move more. Yet obesity is a complex chronic disease, which involves biology, hormones, genetics, environment, medication, sleep, stress, and much more. So the triumph one reminds us that even when we address the biology of obesity, we can achieve outcomes that were once that impossible without surgery. And we're entering a new era of obesity treatment.

[00:13:38] And I believe the next five years may completely transform how we care for patients living with obesity. Thank you so much for joining me for today's episode. If you found this episode helpful, please share it with a friend, family member, or healthcare professional who wants to stay informed about the latest advances in obesity medicine. And be sure to subscribe next week, and I'll be covering another exciting ADA presentation.

[00:14:04] And until next time, stay strong, stay committed, and stay consistent. And remember, we are stronger together. And be sure to subscribe. Bye. Bye.