Physical Activity in Older Adults; Oral Obesity Medication

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include xylazine-laced fentanyl, hepatitis C treatment, oral semaglutide for obesity, and improving physical activity in older adults.

Program notes:

0:35 Improving physical activity for older adults

1:35 Improves susceptibility to chronic disease

2:35 Benefits even beginning later in life

3:33 Oral medication to treat obesity

4:32 Effective in reducing weight with oral semaglutide

5:30 A lot of competitors emerging

6:25 Hepatitis C virus clearance cascade

7:25 1.7 million having been infected

8:26 Oral medication results in clearance

9:17 Fentanyl with xylazine

10:20 The monthly percentage increased to 11%

11:10 Test strips available

12:11 End

Transcript:

Elizabeth: How are we going to get older adults moving?

Rick: An oral drug for the management of obesity.

Elizabeth: Who is getting treated and not treated for hepatitis C infection?

Rick: And adulterants in illicitly made fentanyl.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I think we should start in honor of the fact that you’ve been cycling for the past week with Health and Human Services’ Physical Activity Guidelines for Americans Midcourse Report titled “Implementation Strategies for Older Adults.” This mid-course report takes a comprehensive look at what are older adults, and that would be those 65 and older, doing to keep themselves physically active and how can we improve that, which is really the most important thing.

We have talked so many times about what these physical activity guidelines recommend, so I’m not going to actually go to those recommendations again. The fact is, though, that very few people actually meet those guidelines that include both aerobic and weight-bearing exercise. About 15% of older adults meet those guidelines. As they get older, that activity decreases. Well, we know what the consequences of that are — lots and lots of chronic disease, all kinds of susceptibilities to things that most people would prefer not to have.

This report says, well, what are these barriers that older adults have to getting or staying physically active and then how can we implement things that are going to help to address that. They identify capability-, opportunity-, and motivation-related barriers and they approach this report with community design, policy, systems, and then for individuals, cognitive and physical activity counseling, and finally the implementation of programs that would help to get people involved in these kinds of activities.

Rick: Elizabeth, even though you’re not going to mention what the guidelines are, I am. We are still recommending between 30 and 60 minutes of exercise 5 days a week. That’s 150 to 300 minutes of moderate to, at most, vigorous exercise.

Now, most people over 65 are thinking, well, maybe they’re going to pare it down. No, they’re not at all, because those benefits accrue even if someone starts exercising later in life. The motivation-related barrier is do they have the knowledge to know what to do and the perception that it’s not too late to start.

As you mentioned, there were capability-related barriers, because oftentimes they have chronic diseases, but also opportunity-related barriers because oftentimes they’re socially isolated. They don’t have access to spaces or equipment, or neighborhood environments. This outlines very well how anybody, regardless of what their ability or their opportunities or their motivations are, what can they do to improve their overall health. This is a magnificent and very comprehensive analysis.

Elizabeth: I would just mention that even though you spent the last week on your bicycle — and I spent a lot of time on a bicycle — both of us still need to implement muscle-strengthening activities into our general regimens, because the benefits of those are well established.

Rick: You’re right, and they recommend that we do that at least twice weekly. The core strength is something that even older individuals need to pursue.

Elizabeth: Where would you like to go from here?

Rick: Let’s go to The Lancet and I have teed this up as an oral medication to treat obesity. It’s not a new medication, though. This is a medication that’s been in the news quite recently, semaglutide. It’s called a glucagon-like peptide-1 analogue, or GLP-1 analogue, originally used for people with diabetes. But what we noticed is when we gave it, and it’s given subcutaneously by injection, these individuals experienced a significant amount of weight loss as well. It’s the newest craze. Unfortunately, many individuals don’t want to take injections. They either can’t give it to themselves or don’t want to. To have an oral alternative, it would be very attractive.

This is a study that looked at using oral semaglutide, 50 mg taken once a day, in adults with overweight or obesity. It’s a randomized, double-blind, placebo-controlled, phase III trial to see whether it’s effective or not and what are the side effects.

There were 667 people randomly assigned to either placebo or to oral semaglutide. Was it effective in reducing weight? In fact, it was. More participants reached the body weight reduction of at least 5% — 85% of those taking semaglutide versus only 26% taking placebo.

Then if you’d looked at even 20% weight loss, which is a tremendous amount, a third of the individuals taking the oral semaglutide lost that amount of weight and only 3% in placebo. By the way, it improved blood pressure, C-reactive protein, cholesterol, and raised HDL [high-density lipoprotein].

The only side effects are gastrointestinal, usually mild. Usually as you’re increasing the dose, a little bit of nausea, sometimes vomiting, or constipation. But most individuals tolerate it and they get over it. This is great news that taking a subcutaneous medication and having an oral derivative is just as effective.

Elizabeth: Really good news, of course, because we know that even right now there are shortages of the subcutaneous drug in this country. So many people seem to be waiting for an opportunity to use it. It seems to me that there is also an awful lot of competitors to this drug that are just hanging in the wings, waiting to be either through their phase III trials or other formulations of existing drugs. I think that’s good news, too.

Rick: There are currently three GLP-1’s approved by the FDA for use in the United States, and all of them are given by subcutaneous injection. The advantage of the subcutaneous injection is you can give it once weekly or once every other week — perhaps once a month. Some individuals may prefer to do that. It looks like we’re going to be having many alternatives available, and as you noted, as we get more on the market the price goes down as well.

Elizabeth: Yeah. Because that price is a big barrier for most people. Of course, I just have to say, just like I always say with cigarette smoking, that as far as I’m concerned the place we really need to get to with obesity is prevention.

Rick: It is, but once you’re obese the body tries to maintain that. Even though we lose weight, it gains it back, so having a pharmacologic therapy that can help, I think, is of great importance.

Elizabeth: Let us turn now to Morbidity and Mortality Weekly Report from the CDC. A couple of rather sobering topics, and I’m going to start with hepatitis C virus clearance cascade in the United States between 2013 and 2022.

Hep C is really a success story. My goodness, we are able to cure what previously had been a chronic disease that was often associated with subsequent development of liver cirrhosis and liver failure. Now, we can treat it successfully. There have been massive public health campaigns out there saying that everybody ought to be tested for their Hep C status, whether you had what was purportedly a risk factor or not.

This report estimates that 2.4 million adults were estimated to have been infected with the Hep C virus in the United States. Between 2013 and 2018, a national strategic plan that was developed called for greater than or equal to 80% of persons with Hep C to achieve viral clearance by 2030. During this time period, a total of over 1.7 million people were identified as ever having been infected with Hep C; 88% of those ever infected were classified as having received viral testing, so that’s pretty impressive, I think. What are your thoughts about that?

Rick: Some individuals were cleared on their own, and some have persistent infection. If you’ve cleared it — i.e., you have antibodies, but no virus — you don’t need treatment. But if you have continued infection, those are the individuals you want to treat. The fact that 88% of people had viral testing is good. Here is what happens after that.

Elizabeth: Only 34% were classified as cured or cleared among these, 69% were classified in that group as having had initial infections, 7% were categorized as having persistent infection or reinfection. What are we going to do about this? Well, as I said, we know that an 8- to 12-week short course of oral-only treatment is recommended and results in greater than or equal to a 95% cure rate, so, goodness, we really need to get this started with most of these folks.

Rick: Yeah. That’s really disappointing that only one-third had evidence of viral clearance — either they were cured or cleared on their own. The message is we need to do a better job of testing and a better job of follow-up with regard to putting people on the right medications.

The thing that was really disappointing to me, Elizabeth, was the group that had the lowest clearance were those that were young — less than the age of 35, and especially if they were self-pay. The individuals that were more likely to have clearance of the infection were those over the age of 60 — about 50% of them — so we need specifically to target the younger-aged individuals.

Elizabeth: It’s hard to account for what the reasons are for younger people not coming forward to be tested and then to be treated. That’s absolutely the group that has got to have some more targeted strategies.

Rick: Speaking of strategies, let’s move on. This is a report that talks about illicitly manufactured fentanyl-involved overdose deaths that have a new adulterant called xylazine that has been detected in the fentanyl.

In 2022, data indicated that more than two-thirds of the reported over 100,000 drug overdose deaths in the United States involve synthetic opioids other than methadone, primarily fentanyl. Unfortunately, what’s happened is there are drugs being cut with the fentanyl that actually exacerbate the possibility that can result in death.

Xylazine happens to be one of them. It’s a non-opioid sedative. It’s not approved for human use. It’s really got, unfortunately, no known antidote. This study assessed how often it was detected in illicitly manufactured fentanyl products in the United States drug supply and whether it was involved in drug overdose.

Xylazine in and of itself can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans. When they looked at illicitly manufactured fentanyl overdoses between January of 2019 and June of 2022, the monthly percentage of illicitly manufactured-involved deaths with xylazine increased 276% to now as high as 11%. It’s concentrated primarily in the Northeast. Xylazine was detected in Maryland in about 28% of the illicitly manufactured fentanyl overdoses, Connecticut about 26%, and Pennsylvania 24%.

Elizabeth: This is very concerning, of course. They also have that tendency to develop what looks like necrotizing fasciitis as a result of this too, right?

Rick: Yep, it causes skin necrosis. The unfortunate thing is because it has no antidote it doesn’t respond to naloxone, which is typically given. That doesn’t mean that we shouldn’t try it, because individuals may have opioids that do respond.

Elizabeth: I’m wondering if there are any efforts underway to develop those test strips that people who use these sorts of drugs can use to determine if some of this is in there?

Rick: You’re right. There are available xylazine test strips that really are highly efficacious in detecting xylazine in drug products. We just need to make them more available now that we know it’s much more prevalent in fentanyl.

Elizabeth: Of course, what we know from previous assessments of this issue is that if it’s prevalent here on the East Coast it is inevitably going to move west.

Rick: Absolutely.This is probably an underestimate. You have to suspect it to test for it and many of the places really weren’t testing for it.

Elizabeth: I guess the upside of this is that it will bring it much more into awareness and people will start paying attention to it.

Rick: Absolutely. We need to do routine toxicology testing. There needs to be test strips available.

Elizabeth: Yes. On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: I’m Rick Lange. Y’all listen up and make healthy choices.