Do you recommend a newer, highly effective anti-obesity medication for weight loss to some of your patients? If so, who makes a good candidate and why?
Yes. The most useful thing is if they have insurance coverage for semaglutide or tirzepatide. That gets to the core challenge here, which is these medicines cost between $1,000 and $1,300 a month, so people typically cannot pay for them out-of-pocket. And insurance coverage is currently not very good. So for most people, they can't take the medicine, because they can't afford it.
The FDA indications for an anti-obesity medication are for a body mass index over 30 kg/m2 or a body mass index over 27 kg/m2 with a weight-related health problem. Well, that's a lot of people! So, since it's so expensive, I tend to focus on patients who have more health problems related to their weight.
The drug has been described as a game-changer for weight loss. Do you view it as a breakthrough in the field?
Semaglutide was the first anti-obesity medication that had a couple of important qualities. It crossed a weight-loss threshold, meaning people lose on average 16% or their body weight. So if a person weighs 200 pounds, that's 30 pounds of weight loss. Some people will lose more, some less. That's a degree of weight loss that is noticeable. That's what fen-phen used to give; that's why it was popular. It reached a level of weight loss that people would say, "What happened to you?" So it is more potent than prior medicines were, one.
Two, it was developed, manufactured and marketed by a big successful company. A lot of the older anti-obesity medications were made by small companies, and they weren't marketed or studied very well. Semaglutide comes from a big company, Novo Nordisk, and they have conducted a number of very well done studies. Tirzepatide (Monjaro/Zepbound) is made by Eli Lilly, and they too have done a number of very well done studies.
And not only did these studies show these medications produce weight loss; now there's a study that shows semaglutide reduced cardiovascular disease risk in people with pre-existing heart disease – a 20% reduction. Well, that's a big deal, because not only do you get weight loss; you're getting cardiac protection. There's another study that shows it helps reduce symptoms in people with heart failure. So now we're looking not just at benefits for diabetes and weight, but other benefits in cardiovascular disease risk and heart failure.
What's really groundbreaking here is that semaglutide is the least effective of these new drugs. Tirzepatide gives 20-23% weight loss and other drugs in phase 3 trials are going to be even better. We're doing studies here on the combination of semaglutide with cagrilintide, which is going to come out in a number of years. It's more potent still. Another medication, retatrutide, is likely more potent still. These medications give the kind of weight loss that previously we only saw with bariatric surgery. There's a total of 150 drugs in this obesity category that are in early trials, and 70 of them are in phase 2 trials, and many work by different mechanisms.
So over the next 10-15 years, the number of medications available for weight management are just going to continue to grow, and they're going to be even more effective than the current ones.
Does this mean the medications will eventually be more affordable?
Yes, but that's going to take years, because they will have to get through phase 3 clinical trials and be approved. But in the future, people will have a range of options so that we can use medications in combinations in ways that if you don't respond to one, you could take another. If you have a side effect from one, another one might counteract that side effect. It's going to look a lot more like hypertension treatment than the approach to weight management that we used in the past.
Semaglutide seemed to grow in popularity overnight after endorsements from celebrities and social media. Has the hype affected the supply for patients who need the medication for diabetes?
Absolutely. Many of my patients cannot get these medicines because there are shortages that are the product of so much demand. These are huge companies, but they don't have the capacity to produce these medicines yet at a level to meet demand. I think what's happened is, the people who get semaglutide and tirzepatide for weight are the people who can afford them. It's not the people who need them the most.
I see patients with BMIs of 45, 50 kg/m2, sleep apnea and poorly controlled diabetes. Oprah gets the medicine, and they don't. It is really a health equity issue at this point. I think the media has taken what is a really important medical advance and has turned it into kind of a celebrity sound bite, "Can you get it? Can't you get it?" sort of thing.
Once you've lost weight, should you stop taking semaglutide?
No, we think of weight now as a chronic metabolic condition, just like diabetes or hypertension or high cholesterol. If you took a blood pressure medicine, and your blood pressure came down, you don’t stop the blood pressure medication… This is the same thing with anti-obesity medications. If you stop the medicine, the weight will go back up.
How does semaglutide work to trigger weight loss?
It works as a GLP-1 agonist. GLP-1 is glucagon-like peptide-1. It's a natural hormone that's made from the intestine after we eat. It does many different things. It helps increase insulin secretion to lower blood sugar after a meal. It slows down the gastrointestinal tract, so food doesn't move along as quickly, which creates a sense of satiety. It works directly in the brain to effect a sense of fullness. People who are on this just say, "Yeah, I eat a little bit of food, and I'm full. I just don't need to eat as much anymore."
What are the potential side effects?
The side effects are predominantly gastrointestinal, so nausea is the most common one. Some people get constipation or bloating. And there's some concern over pancreatitis and gallstones, which could be more serious, but these complications are not that common.
Research is suggesting that taking Ozempic can have unintended effects, such as lower birth control efficacy and curbing alcohol cravings. Are there any other consequences, both good and bad, people should be aware of?
Glucose goes down in people with diabetes. Heart risk goes down.
Many women who are heavy have problems getting pregnant, and then, when they lose weight, their reproductive system works better, and they are able to get pregnant. We've known this in bariatric surgery for a long time. Many women who have bariatric surgery become fertile and get pregnant.
And the birth control efficacy, the question is are there problems with absorption of the birth control pills in women on this medication? It has not been well-studied, and that may be an issue. So we typically talk to women about using two reliable forms of birth control, meaning barrier methods plus oral contraceptives, while they're losing weight, or an IUD is a good form of birth control that that's all you need. And, of course, tubal ligation, that's effective. But for some women, these changes in fertility can be a positive effect.
Curbing alcohol cravings is super interesting. There's emerging basic science in animal models that cravings go down with drugs in this class, semaglutide and tirzepatide both. And there's some early clinical data that maybe that's true in humans. There are ongoing clinical trials using these medicines, not for weight, but for alcohol cravings.
More importantly, I think weight loss can be good for a lot of people. If you have sleep apnea, weight loss is helpful, degenerative arthritis, it might be helpful. In the long run, weight is related to cancer risk.
Are there other societal impacts of these drugs?
People are going to have to start thinking about weight like: What is a healthy weight? Because what's going to happen when these medicines are around is there's the opportunity for anybody to lose 30% of their body weight. How many people are unhappy with their bodies where they are, and they're actually pretty healthy? How many people are going to want to change their body weight, and how are we going to deal with that? How are doctors going to deal with that?
I think it's going to make people really kind of say, "Come on. Let's just think about health, not weight. Let's think about lifestyle and behaviors not at how they relate to weight, but because of health." We should all be eating a little bit better diet, and these medicines maybe help us eat a better diet, because we won't have cravings for foods that are unhealthy for us.
What else would you most like people struggling with weight to know about Ozempic and these other drugs?
I would like, first, for people who struggle with their weight to know it's not their fault. This is a biologic problem, and it can be treated medically, and that Ozempic is not the end all and be all. If they can't get Ozempic because their insurance doesn't cover it, they can try other things, but the future is bright.
