Dulaglutide or Tirzepatide? Worldwide Biopharma Changes

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 Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include dulaglutide (Trulicity) or tirzepatide (Mounjaro), hepatitis C treatment, drugs for fatigue in long COVID, and biopharma changes around the world.

Program notes:

0:38 Migrating biopharma industry

1:36 Early stage development

2:36 Need to replicate studies

3:23 Treatment for fatigue from long COVID

4:25 Fluvoxamine or metformin

5:25 Only fluvoxamine helped

6:25 Only for fatigue

6:35 How treatments for hepatitis C have been used

7:36 Number of people receiving treatment declining

8:36 Need a better system

9:16 Dulaglutide or tirzepatide and patient-reported outcomes

10:17 Quality-of-life metrics

11:43 End

Transcript:

Elizabeth: What’s the difference in patient-reported outcomes between dulaglutide or tirzepatide?

Rick: How prescribing trends have changed for hepatitis C treatments.

Elizabeth: Do we have any drugs that are good for long COVID?

Rick: And how early-stage biopharmaceutical innovation has changed around the world.

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: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: I’ll tell you the one I’d like to start with, Rick, if it’s OK with you, in JAMA, a look at this migrating biopharma industry.

Rick: This is pretty fascinating and something I had not thought about. When we talk about biopharmaceutical innovation, we think about it in two ways. One is it’s a source of national [economy], but it’s also a strategic advantage. As public institutions and in private institutions, we invest in domestic drug research and development. We try to do it at home and keep it at home. What’s happening is awareness is that more of that innovation is occurring not in the United States, but outside around the globe. There was a time where they would just do me-too drugs, the innovation would occur in the United States, but now what’s happening is a lot of that innovation is now occurring across the globe.

What these investigators did, they examined the changes over the last 10 years, from 2015 through 2025, to look at the country of origin of what are called early-stage biopharmaceutical development programs. And these are the things that look like small molecules, treatments for cancer, infectious disease, neurology.

And what they discovered was in 2015, 47% of that occurred in the United States, about 6% in China, and the rest in all other countries. Fast-forward to 2025, now the United States has decreased to 38%, 27% in China, and the rest across the rest of the globe.

Elizabeth: This is a national security issue, maybe never more in focus than it could be right now, when there are these interruptions in supply chains for lots of things that are going on all across the globe. Not to mention the fact that it speaks to our focus on things and intellectual development and intellectual property.

Rick: By the way, over this time period, it’s doubled. And although it’s doubled, it’s increased substantially more outside the U.S. than inside the U.S. That puts us behind the eight ball with regard to these new treatments, number one. Number two is oftentimes we don’t accept the results of studies done outside of our country. We have to replicate those in the United States. So we not only have to increase our innovation here, but we have to have ways of partnering with other countries around the world so that we can either do studies jointly, or we have ways of monitoring how their studies are doing and the results, or taking the results and allowing those to be applicable to the approval of drugs here in the United States. So a lot of implications regarding this.

Elizabeth: I think there are a couple of other wrinkles that we should consider: the stymieing of NIH funding. Also, what is going to be the impact of AI [artificial intelligence]? I just saw this week a report of an innovator in this drug-discovery realm who’s actually in South Africa, interestingly, and employing a lot of computing strategies in order to enable him to do these sorts of investigations.

Rick: Yep. So the first thing is realizing how it’s shifted across the globe. The second is, as you suggest, how do we respond to it now?

Elizabeth: Speaking of drugs, then, let’s turn to Annals of Internal Medicine, a problem that, of course, arose with the pandemic for some people, and this is in patients with long COVID.

This study is examining whether fluvoxamine, an SSRI [selective serotonin reuptake inhibitor], or metformin, as we’re well aware, a very old and effective drug for diabetes, can help in ameliorating the effects of long COVID. There’s precedent for both of these in that fluvoxamine has been shown to have anti-inflammatory properties and reduce hospitalization risk in acute COVID, and metformin showed promise in preventing the onset of long COVID in a previous randomized trial.

So this trial examined its role in 399 adults with fatigue secondary to COVID infection persisting for 90 or more days, and they did confirm that this was the precipitating event for the onset of fatigue. The participants were randomly assigned to fluvoxamine 100 mg twice daily or metformin 750 mg twice daily or a matching placebo for 60 days. And what they were looking at was a change in the Fatigue Severity Scale score. Only fluvoxamine showed a significant reduction in fatigue compared with the placebo, and that was evident at day 60, and there was a sustained effect at day 90. It also improved quality-of-life scores.

Metformin, however, showed no significant benefit. The adverse events were really more or less, I would have to say, kind of equivalent in the same range with fluvoxamine (20%), metformin (29%), and placebo (29%). So it looks like fluvoxamine is worth trying, but not metformin in this group of folks with long COVID and fatigue.

Rick: Yeah. And when we talk about long COVID, we’re talking about people that have had fatigue for at least 90 days. A really good study because this is, to my knowledge, the first study we’ve had that has investigated a drug that’s been successful in addressing long COVID symptoms, specifically fatigue. And as you mentioned, we know that vaccinations decrease the risk of long COVID. We know that metformin decreases the risk of long COVID. But once a person’s developed it, we’ve not really looked at any treatments that have been successful in addressing it or treating it.

The only caveat about the study was it was conducted entirely in Brazil at 22 different sites there, outpatient medical sites. So one would hope that the results would be applicable to patients in other countries, like the U.S. or in Europe. This should at least be an impetus for testing it outside Brazil.

Elizabeth: I do applaud the authors for putting their fingers on this notion that the observed benefits may reflect improvements in overall well-being, symptom perception, or functional capacity. And they admit that they did not evaluate whether these effects are causally linked or mediated through specific biological pathways. And it would sure be nice to understand the mechanisms.

Rick: And they also didn’t look at other symptoms. We know the other symptoms like brain fog and other things. So this specific medication is for this specific indication for fatigue. But if you’re the person with it, whether it actually improves it or it changes your perception, it’s still a benefit.

Elizabeth: I agree. Back to JAMA then.

Rick: How treatments for hepatitis C, specifically antiviral agents, have changed over the last 10 years. The first available antiviral agent for treating hepatitis C became available in 2013. It’s a really good story because these are agents — now there are several agents available — that treat different genotypes, but they’re all well-tolerated. They result in a cure in more than 95% of individuals. And prior to their release, we didn’t have any way of treating hepatitis C, which can lead to a chronic condition, cirrhosis, and liver cancer.

What we have discovered, unfortunately, is that only about a third of people in the U.S. with hepatitis C infection actually received treatment within a year of diagnosis. That means that an estimated 2.5 to 4 million people remain chronically infected. The incident cases of hepatitis C have increased during the last decade. There are a lot of people that are untreated. The incidence is increasing. The number of patients being treated would have increased more recently.

Well, unfortunately, what this study shows is that’s not the case. Since 2013 to 2025, there have been an estimated 1.3 million courses of antiviral agents that have been dispensed for treating hepatitis C, the highest number of cases treated, or courses, 185,000 in 2015, and only about 68,000 in 2025.

Elizabeth: I wonder if people understand, and there has been that public health campaign to try to get people to even be tested for their seropositivity for hep C so that they know they ought to be treated.

Rick: Everybody should be screened at least once. If you’re in a high-risk category, you might acquire it later, you may need to have repeated testing. But everybody needs to be tested at least once. You don’t want to be undetected. But even when it’s detected, many of those individuals either aren’t referred for treatment, or they are, but the system isn’t set up to follow up and make sure that the treatment is completed. So we have a lot of work to do.

Elizabeth: It sounds like you’re then putting your finger on the system, that there ought to be a much better systematic approach for identifying these folks and following them up.

Rick: There’s no question about it. I mean, we need to address it in a lot of ways. One is we need to, first of all, assess it. It would be nice to have point-of-care testing so that when you walk into a doctor’s office, they can tell you — your primary care physician, you don’t have to go to a hepatologist — they can tell you, and they can start treatment there. They can give you the prescription. You’re not sending off a lab test, trying to call somebody back and get it done.

And for the person that’s asymptomatic, they say, “Well, why do I need to take this? I don’t feel any symptoms now.” But the symptoms will come later when they develop cirrhosis or liver cancer. So there are a lot of things in the system that need to change to make a very effective treatment more available to individuals that need it.

Elizabeth: Finally, back to Annals of Internal Medicine. Let’s take a look at, gosh, with all those GLP-1s out there, if you’re a person with type 2 diabetes who is already taking them, should you accelerate your dulaglutide or switch to tirzepatide? And this study takes a look at patient-reported outcomes, health-related quality of life.

This was a study that’s known by the acronym SURPASS-SWITCH, a phase IV, randomized, open-label trial in adults with type 2 diabetes. And in this trial, switching from 0.75 mg or 1.5 mg of dulaglutide to 15 mg or the maximum tolerated dose of tirzepatide, compared with escalating to 4.5 mg or the maximum tolerated dose of dulaglutide, they looked at hemoglobin A1c, body weight, and then they reported all of these patient-reported outcomes, including the impact of weight on self-perception, on quality of life, on their ability to perform physical activities of daily living, the emotional impact.

And the upshot of the whole thing is that patients reported improved emotional effect of diabetes treatment at all. Those folks who were treated with tirzepatide felt much more hopeful, optimistic, happy, self-confident, and good about themselves in comparison with their previous treatment. After switching to tirzepatide, more participants felt much more in control of their diabetes, eating, and weight compared with their previous treatment. So it sure seems to be making an argument for making the switch.

Rick: Yeah. So again, these were quality-of-life issues and how do you feel about yourself? I’m not sure that you mentioned that when you compare the two treatments, there was a bigger reduction in hemoglobin A1c — that’s better diabetes control — and more body weight loss with tirzepatide treatment compared to dulaglutide. This confirms not only are the physical outcomes better, but also the quality-of-life outcomes are better as well.

Elizabeth: Right. And since there’s so many choices out there with regard to this, I think it’s important to take a look at some of these measures to help inform that decision.

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

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