95: Semaglutide & Tirzepatide: Revolutionizing Obesity Treatment Beyond the Scale

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I recently came across a podcast featuring Jillian Michaels—the trainer from The Biggest Loser (arguably one of the most problematic shows in television history). During the episode, she reiterated the same outdated message: weight loss is simply about motivation, eating less, and moving more. Listening to this was frustrating, especially considering that two respected physicians in the obesity medicine community were trying to introduce a more evidence-based perspective, but it seemed to fall on deaf ears.

It’s clear that we need to move past these outdated ideas and start focusing on the science that’s shaping our current understanding of obesity. Research is consistently revealing that chronic obesity is not just about willpower—it’s a complex, multifaceted condition that operates differently than simple weight management.

In this blog, we'll explore the latest scientific research on obesity, including how metabolic and hormonal responses to weight loss differ for those with chronic obesity, as well as the benefits of GLP-1s and GIPs that go far beyond weight loss alone.

The Science Behind Chronic Obesity: Why It's Different

One of the most important things to understand about chronic obesity is that it isn’t the same as simple weight management. This is something that’s often overlooked in mainstream discussions, like the one I recently heard with Jillian Michaels. But the reality is much more complex, and recent scientific breakthroughs are helping to shine a light on why.

A fascinating study was just published in Nature on November 18, 2024, which dives deep into this very issue. The paper, titled Adipose Tissue Retains an Epigenetic Memory of Obesity After Weight Loss, offers some groundbreaking insights into how chronic obesity impacts the body long-term. The study looked at a rat model and found that even after significant weight loss, there were still lasting changes in the way the body’s genes were expressed. These changes, known as epigenetic changes, impact how proteins are produced in the body, and they don’t just disappear after weight loss.

This research provides strong evidence for something I’ve observed firsthand with patients: when people who have struggled with obesity for a long time lose weight—whether through lifestyle changes or medication—they often experience more rapid weight gain when they stop treatment. This isn’t just about willpower; it’s about how their bodies have adapted over time to a higher weight set point. The epigenetic changes that occur in people who have dealt with chronic obesity simply don’t happen in those who have never struggled with weight.

For many, the hope is that losing weight will be a one-and-done situation, but unfortunately, chronic obesity is a lifelong condition. This new research underscores the importance of maintaining treatment—whether through medication like GLP-1s or lifestyle interventions—because the body’s internal systems are fundamentally altered by obesity. So even when people reach a healthy weight, they often need to keep their lifestyle changes in place to maintain that weight, because the body remembers its "set point."

This scientific validation is powerful, and it helps us understand why approaches like Jillian Michaels’—which promote the idea that simply eating less and moving more is all it takes—don’t account for the complexity of chronic obesity. This is a medical condition that requires ongoing management, and as we continue to learn from new research, it's clear that we need to rethink the way we approach weight loss and obesity treatment.

The Growing Evidence for GLP-1s and GIPs: More Than Just Weight Loss

There has been an explosion of updates from long-term trials and new studies showcasing the growing benefits of GLP-1s and GIPs, especially medications like semaglutide (Wegovy, Ozempic) and tirzepatide (Mounjaro, Zepbound). While these medications are widely known for their weight loss effects, their impact extends far beyond just shedding pounds.

Key benefits of GLP-1s and GIPs include:

• Improved Sleep Apnea: Recent studies show significant improvements in sleep apnea for patients with moderate to severe cases. Since sleep apnea is linked to health risks like heart disease, this is a major breakthrough.
• Reversal of Non-Alcoholic Fatty Liver Disease (NAFLD): GLP-1s and GIPs are reversing fatty liver disease, which has become more common as obesity rates rise. While weight loss has traditionally been the solution, many individuals struggle to achieve it. These medications offer a new, viable option for treatment.
• Reduced Risk of Type 2 Diabetes: One study found that tirzepatide decreased the likelihood of developing type 2 diabetes by an incredible 94%. Since diabetes increases the risk of stroke and heart disease, this is a crucial prevention tool.
• Improved Cardiovascular Health: Studies have shown that tirzepatide reduces the risk of heart failure, offering a new treatment avenue for patients with this condition.
• Enhanced Quality of Life: Patients taking semaglutide have reported significant improvements in their daily lives, including reduced pain (especially knee pain) and better ability to perform daily activities.

The growing body of research on GLP-1s and GIPs is shifting our understanding of obesity treatment. These medications are proving to be powerful tools in managing not only weight but also a range of other serious health conditions, from metabolic disorders to cardiovascular disease. It's time to rethink the way we approach obesity and weight loss, recognizing the broader benefits these treatments offer.

As we look at the broader health benefits of GLP-1s and GIPs, it's important to also consider how these medications impact cardiac health. Dr. Simmon Lee, a renowned cardiometabolic cardiologist, highlights three key ways they help protect the heart:

• Improvement in Endothelial Function: GLP-1s and GIPs help relax the lining of blood vessels, known as the endothelium. This relaxation leads to lower blood pressure, which reduces the overall strain on the heart.
• Release of Atrial Natriuretic Peptide (ANP): These medications stimulate the release of ANP, a hormone that acts like a natural diuretic. ANP helps excrete salt through urine, contributing to further reductions in blood pressure and reducing fluid retention in the body.
• Decreased Inflammation and Cholesterol Levels: GLP-1s and GIPs lower inflammation and improve cholesterol profiles, which reduces plaque buildup in the arteries. This protects against heart disease and enhances overall cardiovascular health.

A lot of people still believe that weight loss just comes down to eating less and moving more, but for many, this simply doesn’t work. There are a lot of complex metabolic factors that make weight loss harder than it seems. The growing research showing improvements in things like heart health, reduced risk of type 2 diabetes, and better management of conditions like sleep apnea shows that the benefits of GLP-1s and GIPs go far beyond just losing weight. It’s becoming clear that addressing these health issues early on is the key to long-term success, and these medications offer a better chance to do that.

P.s. Here is a picture of the studio I was working out of to record this episode of the podcast!