Dr. Kohli On Obesity

The obesity epidemic is a major concern in the U.S., with four in 10 adults now considered clinically obese. Obesity, plain and simple, is terrible for the heart, and ends many lives prematurely. A recent study, published in The New England Journal of Medicine, reported on the efficacy of Tirzepatide, a dual agonist which demonstrated remarkable results in lowering body weight.

DocWire News spoke with our Medical Lead, Dr. Payal Kohli, to glean her thoughts on obesity, the study, and the potentially game-changing therapeutic agent, Tizepatide.

DocWire News: Talk to us about the obesity epidemic, and the impact being obese has on the heart.

Dr. Payal Kohli: It’s gotten so bad that four in 10 adults are now considered to be obese. We know that obesity in and of itself can of course increase your cardiovascular risk because the fat is hormonally active. So, the fat actually secretes hormones that can increase inflammation, adverse cardiovascular events. Where the fat is distributed matters too. So, what your shape is, and a lot of us tend to hold onto fat on our bellies and that central adiposity can really increase cardiovascular risk.

But we also know that obesity can lead to actually other things that can increase cardiovascular risk, other conditions like hypertension, diabetes, sleep apnea, each of which is independently associated with risk. There’s actually some recent data now that has also come out that says even if you’re obese and technically “healthy”, meaning you don’t have any of those adverse cardiovascular conditions today, your lifetime risk just by virtue of being obese is actually substantially higher.

So, the obesity epidemic, I think has hit an all-time high, particularly coming out of COVID. I feel like here in 2022, we really ought to have more better medical options and pharmacologic options to help our patients who are struggling with obesity.

In a recent study, published in the New England Journal of Medicine, Tirzepatide was assessed for treating patients with obesity. Talk to us about this novel therapy, and how it works.

Yeah, very interesting agent. So Tirzepatide is a dual agonist. So, it’s agonist for the GLP-1 receptor. Many of us are familiar with GLP-1s, which were initially sort of developed as a diabetes drug and have now kind of made their way into the cardiovascular space because of their outcomes and risk reduction. So, it binds the GLP-1 receptor, but it also binds a second receptor called the GIP. These are both hormones that are involved in regulation of multiple different metabolic phenomena, actually including regulation of our glucose levels, our lipid levels, our body weight and even our satiety signal. So, they’re involved in then cretin pathway, which can lead to satiety in our brain.

So, by stimulating both of these together, they actually work better together than they do individually, just as a GLP-1 receptor agonist, for example. They work to really help us to feel fuller and to change many of those metabolic things that can lead to weight gain and adverse cardiovascular events.

How was the study conducted, and what were the findings?

So, this was a randomized control trial. It was called the SURMOUNT Trial and what they did is they took about 2,500 obese adults and there were two types of obese adults. So, one was just, you had a BMI greater than or equal to 30. So that got you into the study. But the other type was actually what somebody might not call incredibly obese, but a BMI greater than or equal to 27. But you had to have at least one obesity or weight related condition. So that could include conditions like hypertension or sleep apnea. Notably, diabetes was not allowed as your weight related conditions.

So, they took these two classes of individuals, and they randomized them in a one-to-one-to-one fashion. So, one arm got placebo and the other three arms got three different doses of the study drug. Then they followed them for about 72 weeks. So really nice long trial and they looked to see how much weight was lost. It’s really incredible if you look at the results because people started out at 105 kilograms of weight, which is about 230 pounds. In a dose dependent fashion, they lost 15 to 21% of their body weight. So, you’re talking 35 to 50 pounds of weight reduction with this once weekly injection. 85 to 91% of the people in the study lost at least 5% of their body weight, and more than half of them lost 20% or more of their body weight. So, we’re not talking small progress here. We’re talking big gains in their weight changes and no surprise, all their metabolic parameters actually improved after treatment with this medication.

What I really love about this class of medications, first is that we have outcomes data for the GLP-1 receptor agonist. So, we know that giving people these medications doesn’t just help them lose weight as in this trial, but it can actually also improve their major adverse cardiovascular events and minimize the risk of heart attacks and strokes and so on and so forth. But the second thing that I like is that they’re really well tolerated. Now they work on our satiety signal in our brain. So, we did see some GI side effects, mostly nausea, and they mostly occurred when the dose was being kind of escalated. So, you start people out slowly and you slowly increase the dose so that you don’t just slam them with the highest dose. But for the most part, people were able to stay on these medications and tolerate them. I think it’s really opened the door to have this discussion that we’re having about how we treat obesity in 2022.

What are the clinical implications of these findings as it pertains to the fight against obesity?

I mean, I think that it’s really changed the paradigm for treating obesity and has changed it from just a disease that you have to figure out. For the last 20 years or so, we’ve really just had diet and lifestyle, and that’s what we tell our patients who are struggling with this disease of obesity. We tell them do more exercise and eat less. Now we have these really incredible medical options and in fact, as a result of this trial and others, the FDA has actually greenlighted this particular drug for consideration under new drug application approval.

Now, there are other studies ongoing with this drug in the diabetic population also because as I said, it was initially designed as a diabetic drug. We also have another drug Mounjaro, made by another manufacturer that already does have FDA approval for the diabetic population. But I think in a year or so, we’re really going to be looking at a new way to think about how to treat obesity.

Any closing thoughts?

I would just add that each and every single one of us as healthcare providers really ought to start thinking about obesity as a medical disease, including for ourselves and our family members. Really acknowledging it and treating it head on because the domino effect that occurs from obesity and all the other things that we’re trying to treat, we end up having a very reactive approach rather than a proactive approach. I think medications like this have kind of opened the doorway for us to think about how we can prevent the onset of many of those other conditions, even in our younger patients.

So, I, for example, have started talking to friends and family members and patients of course, who are young and technically healthy because they haven’t developed their hypertension, or their diabetes, or they sleep apnea yet, but they’re overweight and they’re struggling to lose weight. I think these types of drugs, if they do get FDA approval, will really help us to empower those types of individuals to get that weight off.

The other thing I would add is that this is not just a one and done treatment. So, it’s not something you just start and then you can stop. It would be a chronic treatment. Just like we think about treating hypertension, or diabetes or hyperlipidemia chronically, that’s how we want to think about treating obesity longitudinally over time.