Jul 13, 2022

Interviewer: In spring of 2022, there were some headlines going around almost every news outlet saying that the FDA had finally approved a new weight loss drug, one that would promised 10% to 25% weight loss with little more than just a weekly injection. The drug is called tirzepatide, or a brand name Mounjaro.

Now, it seems a little too good to be true. So, today, we're going to be looking at what exactly is the drug and what can it actually do for weight management.

Joining us today is Juliana Simonetti. She is the medical co-director of the Comprehensive Weight Management Program at U of U Health. So she knows a thing or two about weight management.

Dr. Simonetti, thank you so much for joining us.

Dr. Simonetti: Yes. Thank you so much for having me here today. I'm very excited to be talking about this new drug.

Interviewer: So why don't we start there? What is tirzepatide and what does it do to the body?

Dr. Simonetti: I'll start by just telling a short story. I was at an endocrine meeting in California two weeks ago when this drug got approved by the FDA for the treatment of diabetes. And we were doing a lecture, and all of a sudden, everyone started clapping and announced that this drug had been approved by the FDA for the treatment of the diabetes. So that's the kind of excitement we're getting with this drug.

It is a new class of medication for the treatment . . . Currently, it's only approved for the treatment of diabetes. However, we have seen really significant amounts of weight loss with the medication, and they are doing clinical trials at this point, and they have the results of the clinical trial for the treatment of obesity with this drug as well.

Tirzepatide is unique in the sense that is a dual incretin medication. It attaches to two different receptors. So we have a class of medication that has been in the market now for about 15 years called GLP-1 receptor agonist. And some of the drugs I think are well known at this point, both for diabetes and for weight loss. All those drugs were initially developed for the treatment of diabetes, and then they found that they led to significant amounts of weight loss.

So some of the drugs currently on the market that are GLP-1 receptor agonists are Victoza, Ozempic, Trulicity, and those drugs really have revolutionized the treatment of diabetes in the sense that they bind to receptors in our body that stimulates our own pancreas to produce insulin. And at the same time, they cross the receptors in our brain and tell us that we're full.

Therefore, when you start eating, you feel fuller sooner. It leads to induced satiety, so therefore people eat less, and it promotes the release of our own insulin so you have better glucose control, better sugar control for the treatment of diabetes. And we have this induced satiety that leads to people eating less, feeling fuller, and therefore losing significant amounts of weight.

Interviewer: So tirzepatide has been approved by the FDA to help manage and treat types of diabetes. But there's a lot of evidence in their, I guess, Phase 3 trials that are showing real potential to help with weight loss. What are they finding?

Dr. Simonetti: That's right. So their clinical trials for diabetes show . . . for those participants that had diabetes, it led to a significant amount of weight loss. And so they also then did clinical trials for this medication for those without diabetes for the treatment of obesity.

And what they found is that they highest dose of the medication, which is 15 milligrams, can reduce body weight on average by 28.4 pounds, which is nearly about 14% of the total body weight. So, for someone that weighs about 200 pounds, they will lose on average of about 28 pounds on this medication, which is really, really significant.

Interviewer: Wow. That sounds like a lot of weight loss for people without diabetes, but what does it do for people who do have type 2 diabetes? What kind of results have they been seeing with them?

Dr. Simonetti: Yeah, the results, it's really interesting because the results for those with type 2 diabetes, on the highest dose, show that those participants lost almost 21% of their total amount of weight, which is really, really impressive. This is more than anything else, any other medication we currently have in the market.

Interviewer: So if I get this correct, there are other . . . I've seen other drugs out there that fill your stomach up, the Plenity or whatever it's called, or they claim to impact your metabolic system, etc., but this drug actually impacts your pancreas in a way to help with glucose levels and help suppress hunger.

Dr. Simonetti: Yes. So the class of medication I was talking about is the GLP-1 receptor agonists that already exist that have been in the market now for about 15 years. The newer ones, one of them being semaglutide, or the other name is Ozempic, has been the latest.

They also got approved for the treatment of obesity and leads to very significant amounts of weight loss and improvement in the sugars in our blood because it stimulates the pancreas to release insulin and tells our brain . . . So it works on the appetite centers of the brain.

The difference between some of these drugs and what you're talking about, Plenity . . . So Plenity is considered a device because it's three capsules that kind of inflate in your stomach and therefore makes you feel fuller, so you have the physical sensation of fullness. However, the GLP-1 receptor agonists work in your brain and in the appetite centers of the brain. It works in the brain to tell you that you're full, so you don't have those cravings and then sensation that you wanted to keep on eating. It really leads to the feeling of feeling fuller.

With tirzepatide, why this is so exciting and different is that this not only works with the GLP-1 receptors, but also works in another receptor called GIP, which is a glucose-dependent insulinotropic peptide. It's a mouthful, but it's really another hormone in our body that is usually . . .

Both of those hormones are released in response to us eating food. So when I eat carbs or sugar, it goes in my stomach and then reaches my stomach and my intestines, my gut. My body says, "Whoa, we got nutrients here." We release the GLP-1 and this other one called GIP hormones that then say, "We got food, we got carbs, we got sugar. Let's tell our pancreas to release insulin," because we just got some food in our body. We got some sugar in our body. And then it crosses the brain and tells the appetite centers in my brain that, "I just got nutrients. We should stop eating." It should make me feel a little fuller.

The issue with our natural hormones in our body is that they get taken down, they get broken down very quickly. They only last a few seconds. And these new drugs bind now to those two different kinds of hormones and lead to this really much heightened sensation of fullness and to a much more significant response lasting much longer than what our own body would produce.

Therefore, that's why they're so effective. And therefore, that's why they are also given once a week, which is really kind of neat for a lot of those medications. So you don't have to take a medication every day. It's a small injection once a week.

Interviewer: Wow. So I guess when I first came into this interview, I'm used to doing stories about how some new drug that came out is not actually going to help you with weight loss when you really look at the research. But with your professional opinion, as a doctor who works with patients suffering from obesity or helping them live healthier with their weight management, why is this drug so exciting like you keep saying?

Dr. Simonetti: It is so exciting because the amount of weight loss we are seeing with the clinical trials from this drug is much more significant than what we had seen previously.

So as a measure for FDA approval for a drug for weight loss is usually about 5%. And with the latest drug, which is semaglutide with the other name of Wegovy, we saw a significant more amount of weight loss, around 14%, 15% with the higher doses. And with tirzepatide, we are seeing weight loss of around 20% with the higher dose of the medication, which 20% is a lot of weight, right? So it's a really significant amount of weight loss that we are seeing with these new classes of medication.

And as we know, weight loss is extremely difficult, right? This idea that if we just diet and exercise, we should just be able to lose weight. And it's not true. Eighty-five percent of those that diet and exercise actually, unfortunately, end up gaining the weight back and this weight loss is not sustainable.

And there are a lot of reasons for that, right? There is genetics. So 60% to 70% of the way we are, we know that it's related to genetics or the way we accumulate fat.

There's also our environment, and then there is this regulation in a lot of the hormones. There are these regulation appetite hormones. There is this regulation with insulin. The more weight that we gain, the more insulin-resistant we become. Therefore, there is this combination of insulin resistance.

So 90% of those that have diabetes also have excess weight. And some of the older medications that we had for diabetes, like the glipizide, glimepiride, and even insulin would lead to more weight gain, which then meant more insulin resistance and then making the condition just worse.

And with these new drugs, we see significant improvement in weight. Therefore, you also see significant improvement in decreasing in insulin resistance and also improvement in the glucose control and the sugar control in the blood because it works in conjunction. You have the stimulation of the pancreas and decrease in appetite.

Reading through the clinical trials again, and I just had done a quick review before we sat down for this interview, really it's quite impressive. One of their trials, they compare this drug for participants that have diabetes that were taking insulin and they gave them the tirzepatide. And those that took the tirzepatide lost weight versus those that were taking insulin actually by itself gained weight. So this is, again, quite significant in the amount of weight loss as well as in the amount of glucose control that we get with this medication.

Interviewer: So for all of the people who are thinking, "Oh, hey, this is the drug that's going to make me lose all my weight, finally," it's not ready for them, right? Is that what I'm understanding correctly?

Dr. Simonetti: That's right. So this medication is not yet approved for weight loss. I believe it will be, hopefully, within the next year or two. They are just finishing the Phase 3 clinical trials for weight loss.

Currently, this medication is approved for those with diabetes, and I think it'll be a wonderful tool for those that have diabetes and excess weight, overweight or obesity. This would be just a wonderful medication because it leads to a significant amount of weight loss and improvement of their diabetes.

This is great, and I think this is going to really improve the care that we can provide. However, we need to remember that obesity is such a complex disease, right? There's a multitude of issues that go with it. So this is addressing maybe some of our physiology, but we still need to do lifestyle modifications with modifications in our diet, increasing physical activity.

Behavioral health is a really important piece. Oftentimes, we eat in response to feeling sad, depressed, because when we eat in particular foods that are sweet or high caloric foods, it releases dopamine and serotonin in our brain. So it actually makes us physically feel better at the moment. And therefore, we go back and eat more because then I need another hit and then I feel better. And it becomes that very vicious cycle that once you start eating certain things . . . know for me, it's a piece of chocolate, right? I'm having a bad day at work, I eat a little piece of chocolate and my life is better at that moment. However, that doesn't help me because then my sugars crash and it makes me want to crave it more.

So really trying to address as many things as possible, and that's why in our program, we have this multidisciplinary team approach. We have the registered dieticians. We have an exercise physiologist. We have two Ph.D. psychologists. We also have other options such as surgery. So we work with the bariatric surgeons.

So again, it's wonderful to have one more tool, a very effective tool in our toolbox, but this is a tool. We are able to use it, and the more tools that we have, I think the better offer we're going to be, but we have to address all these other pieces as well.

Interviewer: So, obesity, it is not as simple to treat as just getting a new injection, even with some of these great new drugs. So I guess we'll just keep a look on the headlines, see if this is approved for obesity treatment in the next couple years, and maybe we'll have you back on and we can talk about how you guys can utilize it in your toolbox to battle obesity.

Thank you so much for joining us, Dr. Simonetti. I really appreciate you taking some time to talk to us about this new drug.

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