How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Teenagers who use cannabis have a dramatic increased risk for a psychotic disorder, compared with their counterparts who don’t use the drug, new research showed.

Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.

“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.

“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.

The study was published online in Psychological Medicine.


 

Increased Potency

“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.

The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.

To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.

They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.

Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.

The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.

Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
 

Perception of Harm Declining

When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).

“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.

The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.

The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.

Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.

Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.

This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45. 

Colorectal cancer cases increased 333% among 15- to 19-year-olds and 185% among 20- to 24-year-olds from 1999 to 2020, according to new research presented at the annual Digestive Disease Week^®. 

As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.

Some Risk Factors Can Be Changed

The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.” 

“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.

On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
 

Risk Varied by Age

In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a

• 68% increase for ages 25 to 29.
• 71% increase for ages 30 to 34.
• 58% increase for ages 35 to 39.
• 45% increase for ages 40 to 44.

“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”

The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk. 

“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”

A version of this article appeared on WebMD Health News.

WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45. 

Colorectal cancer cases increased 333% among 15- to 19-year-olds and 185% among 20- to 24-year-olds from 1999 to 2020, according to new research presented at the annual Digestive Disease Week^®. 

As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.

Some Risk Factors Can Be Changed

The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.” 

“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.

On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
 

Risk Varied by Age

In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a

• 68% increase for ages 25 to 29.
• 71% increase for ages 30 to 34.
• 58% increase for ages 35 to 39.
• 45% increase for ages 40 to 44.

“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”

The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk. 

“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”

A version of this article appeared on WebMD Health News.

WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45. 

Colorectal cancer cases increased 333% among 15- to 19-year-olds and 185% among 20- to 24-year-olds from 1999 to 2020, according to new research presented at the annual Digestive Disease Week^®. 

As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.

Some Risk Factors Can Be Changed

The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.” 

“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.

On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
 

Risk Varied by Age

In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a

• 68% increase for ages 25 to 29.
• 71% increase for ages 30 to 34.
• 58% increase for ages 35 to 39.
• 45% increase for ages 40 to 44.

“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”

The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk. 

“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”

A version of this article appeared on WebMD Health News.

TOPLINE:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.