Adam Sturts, DO, is an internal medicine resident at Penn State Hershey Medical Center with an interest in cardiovascular health and endocrinology. Sturts is a graduate of the Rowan University School of Osteopathic Medicine and a type 1 diabetic. 

Adam Sturts, DO

) is the third leading cause of cancer-related death despite only accounting for 3% of all new cancer diagnoses.

 Obesity is a well-known risk factor for multiple types of cancer, including PDAC. In fact, there exists a relative risk of PDAC of 1.10 for every 5-unit increment increase in body mass index (BMI).

 While bariatric surgery has been demonstrated to reduce overall cancer incidence and mortality, conflicting data exist regarding the effects of bariatric surgery on PDAC.

We performed a retrospective case-control study utilizing the National Inpatient Sample (NIS) database from October 2015 to December 2020. All adult subjects (age ≥18 years) with a BMI >40 kg/m2 or >35 kg/m2 with ≥1 metabolic comorbidity were identified and stratified into those with and without a history of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy).

, Tenth Edition Clinical Modification (ICD-10-CM) codes were used to define variables of interest. Baseline characteristics and comorbidities among the 2 groups were compared using chi-squared and Wilcoxon rank-sum tests and logistic regression analysis was performed to assess the risk of PDAC after adjusting for multiple risk factors, including tobacco use, acute and chronic pancreatitis, diabetes mellitus and various stages of obesity.

Over 19 million subjects were included, 1,656,329 of whom had a history of bariatric surgery. Patients with a history of bariatric surgery were significantly younger, more frequently female (75% vs 58%), had higher rates of class 3 obesity (69% vs 52%) and lower prevalence of hypertension, hyperlipidemia, chronic kidney disease, Charlson Comorbidity Index (CCI) ≥3, tobacco use, acute and chronic pancreatitis and pancreatic cancer (0.1% vs 0.2%) while having a higher prevalence of OSA (

 <.001). Additionally, in-hospital mortality (0.5% vs 1.8%), total hospital charges and overall length of stay were lower in the bariatric surgery cohort compared to the nonsurgical cohort (

 <.001). After adjusting for multiple comorbidities and risk factors, history of bariatric surgery was demonstrated to significantly reduce the risk of PDAC on both univariable (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.44 - 0.56) and multivariable analysis (OR, 0.68; 95% CI, 0.61 - 0.77).

This is the largest analysis to date investigating the effects of bariatric surgery on pancreatic cancer risk reduction and serves to clarify previously inconclusive data. We have shown bariatric surgery to exhibit an independently protective effect against PDAC oncogenesis. It is reasonable to suggest that patients at increased risk of PDAC as well as other obesity-related malignancies may be recommended for surgically-assisted weight loss earlier and more frequently.

With advancements in minimally invasive bariatric procedures, expanding patient eligibility and indications for surgery, increasing utilization of bariatric surgery and endoscopic bariatric and metabolic therapies may help alleviate the growing burden of pancreatic cancer.

Surveillance, Epidemiology and End Result (SEER) Program. Surveillance Research Program, National Cancer Institute. 2023 Apr 25. https://seer.cancer.gov.

Aune D, Greenwood DC, Chan DS, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. Apr 2012;23(4):843-52. doi:10.1093/annonc/mdr398

Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort. Ann Surg. Jan 2019;269(1):95-101. doi:10.1097/SLA.0000000000002525

Adams TD, Stroup AM, Gress RE, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity (Silver Spring). Apr 2009;17(4):796-802. doi:10.1038/oby.2008.610

Sjöström L, Gummesson A, Sjöström CD, et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol. Jul 2009;10(7):653-62. doi:10.1016/S1470-2045(09)70159-7

Tee MC, Cao Y, Warnock GL, Hu FB, Chavarro JE. Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis. Surg Endosc. Dec 2013;27(12):4449-56. doi:10.1007/s00464-013-3127-9

Bulsei J, Chierici A, Alifano M, et al. Bariatric surgery reduces the risk of pancreatic cancer in individuals with obesity before the age of 50 years: A nationwide administrative data study in France. Eur J Surg Oncol. Apr 2023;49(4):788-793. doi:10.1016/j.ejso.2022.11.013

Fan H, Mao Q, Zhang W, Fang Q, Zou Q, Gong J. The Impact of Bariatric Surgery on Pancreatic Cancer Risk: a Systematic Review and Meta-Analysis. Obes Surg. Apr 05 2023;doi:10.1007/s11695-023-06570-x

Wilson RB, Lathigara D, Kaushal D. Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk. Int J Mol Sci. Mar 24 2023;24(7)doi:10.3390/ijms24076192

A history of bariatric surgery was associated with up to 50% reduced risk of PDAC among a national cohort.

Bariatric Surgery is Associated with Reduced Risk of Pancreatic Cancer: Analysis of a US National Database

Brian Baggot, MD

Joseph, do you have any final thoughts about, or takeaways from, this discussion?

Education is important for everybody. Many health care providers, including myself, always had this feeling about FMT [fecal microbiota transplant]. Is it dangerous? Will patients wind up getting sick? Where does the stool come from? Is it a mix of donors or a single donor? How much will it cost? And the whole idea of a colonoscopy with bowel prep and propofol, which I mentioned before, seems like a lot. We need to change the way we think about the natural course of 

 infection [CDI]. Hopefully, people will and explore all treatment options that are available at this point.

As far as education with the practitioners, it is about educating the patients as well. If they happen to be frequent fliers for, let’s say, as you mentioned, UTIs [urinary tract infections]. Or they go to their physician, and they say, “I have a cold,” and they’re given an antibiotic. You have to explain to patients as you’re seeing them come into your practice that it’s not important to get an antibiotic every time you go to your physician’s office. And to educate them and not to try to doctor-shop and get an antibiotic if they don’t get the right answer from their primary care physician [PCP] or whomever. It’s important not only for practitioners, but for patients or potential patients for 

 Certainly, we’re going to continue to need patient education, and I appreciate that comment. Andrew?

I am cautiously optimistic now, at this point, as to where we’re headed with CDI treatment, as we have the first FDA-approved FMT product at this point right now with seemingly more on the way. We’ve got the first one through the door, and it’s going to be a matter of seeing where things go from here. As you mentioned earlier, maybe hopefully in the next 10 years we’ll have narrowed it down to which key microorganisms are essential for restoring the microbiota. And if we see these improvements, then hopefully the treatments will continue to become more effective into the future as well.

Appreciate that. I have to say that I’ve considered myself in the past a drug pusher, if you will, in the good sense of the term. But I am excited the fact that there is now an FDA-approved fecal microbiota replacement and that’s a nice, good step forward with assurance that it’s screened and safe, for the most part. And that’s a major step for managing patients with recurrent 

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Experts provide practice pearls for educating patients on and using FMTs for the management of CDI.

Key Takeaways on FMTs in the Treatment of CDI

Candace Cotto, RN

Before we transition out here, any thoughts on the future pipeline, phase 2 data, or phase 1 data, what’s the future here?

There are lots of potential options, more second-generation FMT [fecal microbiota transplantation] products that we can talk about, but we also have other narrow-spectrum antibiotics in the pipeline. The closest is ridinilazole, which is similar to fidaxomicin, and it’s going to target 

 and kill it very well, but also spare our commensal microbiota. The phase 2 data look great, it helped prevent recurrence among patients who received ridinilazole compared to oral vancomycin. That’s exciting to me.

There are 2 other microbiome-based therapies that have finished phase 2 clinical trials and 1 that has finished a phase 1 clinical trial. Going alphabetically, CP101 is a full-spectrum microbiome-based therapy that recently finished a phase 2 clinical trial and showed a 74.5% versus close to 60% success rates. This is going to go to a phase 3 clinical trial in the near future. There’s another one that is a room temperature stable or nonfrozen formulation of a capsule called RBX7455, and that one finished a phase 1 study with a 90% success rate, and a larger trial is being planned at this time. Then finally, moving on to what I call designer microbiome-based therapies, where the field is going to go, is VE303, which is from a donor-independent bacterial consortia. Recently in a press release, they had their phase 2 data presented, where the high-dose VE303 was statistically significant and clinically meaningfully different from the placebo in preventing recurrent 

 infection. There is lots of excitement going on in today’s world.

There’s one more. There’s a company now with a particular single strain of bacterium that thrives on a particular oligosaccharide that’s found in certain kinds of fibers where they’re hoping that this 1 strain, which would be a true probiotic, would be able to reduce the risk for recurrences of 

 We’ve really painted the entire spectrum of all the different therapeutic options. We start with full-spectrum stool, which is basically the entire biodiversity. We move toward another company that basically focuses on the different consortia, or the ecological niches, where defects in metabolism can then just be plugged right back in. Then we have these companies that are more designer that have found out that maybe we can pick this handful of species alone and give them back to our patients. And then companies that are probably more savvy have figured out that there may be some species that have multiple functions, and you may just need to give 1 species back. And of course, as we are scientists, we can figure out what we don’t need to give an organism back, we can just find the products that they produce or the proteins that are on their surface and use those. There’s a whole different spectrum of therapeutic options, which is great for our patients because at that point, we have options to choose what’s going to work best for patients in different scenarios.

So the future is bright. I would like to ask all of our participants to give us a final thought.

One of the things that we sometimes neglect is how devastating this disease is to our patients. We talked about the diarrhea itself, we talked about the hospitalization, the epidemiology, the impact on hospitals, but at the same time, there are a number of patients who have their lives turned upside down because of the first infection or the recurrences. I’ve taken care of patients who have lost their jobs, I’ve taken care of patients who can’t be with their families, who ask me if they can see their grandchildren. I’ve seen patients who have developed this post-traumatic stress disorder from having 

 infections. If we think about the thousands and thousands of recurrences that we see each year, there are thousands and thousands of people who are not the same after this infection. I’d like to stress to everyone who’s watching to read these guidelines and look to see what is the appropriate way to treat these patients the first time because that gives them the best chance of success of beating this infection so that they can go back to their normal lives afterward.

That was beautifully said, Carl. This infection creates a huge burden on individual patients, but also on our health care system. I’d also like to mention that the microbiome field and microbiome therapeutics are burgeoning right now. We are learning new things every single day, and some of these microbiome-targeted therapies are ultimately going to be studied in other diseases too, so hopefully, we can make an impact elsewhere in addition to 

 infections. And the last thing I’ll say is, eat your fiber and close the toilet lid when you flush.

I’ll add 2 things. One thing to add to Carl’s point that is paramount is educating our patients on the impact of this illness. When you see a patient for the first time, don’t just hand out an antibiotic prescription and say, “You’ll be fine.” Patient education is paramount. There are resources that are available at the CDC’s [Centers for Disease Control] website, NIH [National Institutes of Health] has resources, and also the C Diff Foundation is a tremendous resource that I suggest to my patients. The other point that I would make is that as these microbiome-based therapies become mainstay, they’re going to move from tertiary care centers, from infectious disease and GI [gastrointestinal] doctors to empower primary care providers, family practice providers, nurse practitioners, physician assistants, who are the first touchpoints that our patients sometimes have with recurrent 

 They should start thinking that they should be and will be able to prescribe these therapies to our patients.

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Closing out their discussion on Clostridioides difficile infection, panelists share closing thoughts on novel pipeline therapies.

Looking Toward the Future of CDI Management

Carl V. Crawford, MD

 Javed, the last couple of points I’d like to touch on before we close speak in part to the continued development of the space. There are a couple of therapies that you mentioned earlier that I’d like you to give a 30-second bullet on for each, which includes vericiguat and intravenous [IV] iron. In the landscape of therapies for our patients with heart failure with reduced EF [ejection fraction], where do these fit in? Do they fit in at this point? Where do you see them going in the future?

 Think about the journey of patients with heart failure. You have no heart failure, then you develop heart failure and you’re not on any therapy, so the risks are pretty high. Then you get started on the standard therapy and the risks come down—what we call residual risk—but it’s never back to not having heart failure. Then you start breaking through, you start developing worsening symptoms. Whatever therapy you were taking that kept you stable as an outpatient is not enough anymore. That is now an entity we call worsening heart failure.

We did the VICTORIA trial on vericiguat that had a positive result on the cardiovascular death and heart failure hospitalization primary end point. It was focused on people on standard therapy who developed worsening heart failure, either recent hospitalization or the need for outpatient IV diuretic. That therapy is now approved by the FDA for ejection fraction less than 45% and recent worsening heart failure because of improvement in cardiovascular death and heart failure hospitalization. Whether it should be given to people without worsening heart failure is something we are all questioning. Let’s see if we can generate some evidence.

I really like IV iron because this is a specific disease within heart failure that you’re treating. Iron deficiency should be in our minds dissociated from anemia. There are other causes of anemia, but iron deficiency, regardless of anemia, is associated with worse outcomes. Anemia reduces oxygen carrying capacity, but iron is also needed for ATP [adenosine triphosphate] generation in the mitochondria. You can have reduced energy production, regardless of anemia, as well. We had a lot of trials in the outpatient setting showing in the past that iron-deficient patients given IV iron improve quality of life and functional capacity. Now we have a 1-year outcomes trial called AFFIRM-AHF. When patients in the hospital setting with iron deficiency are given iron, you reduce the risk of rehospitalization in those patients. This was an outcomes trail, and not only a quality of life and functional capacity trial.

In whom would you suggest IV iron be considered? Can you give us a transferrin saturation number?

Yes. There is an issue of absolute iron deficiency or relative iron deficiency. If a patient has a transferrin saturation of less than 20%, that’s a good patient to get iron. But remember that oral iron therapy, unfortunately, does not get absorbed very well, so you have to give IV.

 Yes, I was going to actually ask, “Why don’t we just throw some iron sulfate into the medical program?” You just jumped ahead of that question. It’s a really important consideration that clinicians need to know, in part because patients with heart failure don’t absorb PO oral iron as well due to abnormalities of hepcidin.

I’m going to draw this to a conclusion and try to appeal to our viewers, which include a large number of community physicians, to remember that heart failure is a team sport. We need to work together in understanding how to identify these patients, how to initiate therapies, when to initiate therapies, and when to reach out for help. In the expert consensus document, I would ask you to have a look at 1 specific figure that focuses on recognizing heart failure, initiating the therapies, but then recognizing when patients are not responding and where you might need to kick it up a notch and refer to a heart failure specialist like Dr Butler.

There’s a simple acronym called I-NEED-HELP. Each letter refers to a different aspect of struggles in heart failure care that might help you recognize when to reach out to an advanced heart failure specialist. Not every patient with heart failure can be treated by a heart failure transplant specialist. The care of our patients most in need to reduce their risk for heart failure events is in your hands. The American College of Cardiology and the development of this expert consensus decision pathway document recognizes that. In addition to the document, there’s a smartphone application called TreatHF that summarizes all of the things that we just talked about in terms of the therapies, how to use them, when to use them, how to troubleshoot adverse effects, and other issues that come up in the course of the care of our patients with heart failure. It’s all in your hands, folks. We hope that the document is as useful to you as it is for us. Dr Butler and I both find it to be a really helpful piece of support for the care of our patients. 

I want to thank you all for watching HCPLive® Peers and Perspectives®. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peers and Perspectives® and other great content right in your inbox. Javed, thanks so much for spending time today.

James Januzzi, MD, and Javed Butler, MD, MPH, MBA, discuss emerging agents, vericiguat and intravenous (IV) iron, in the treatment landscape for heart failure with reduced ejection fraction and advice for community physicians managing patients with heart failure. 

Emerging Agents for Heart Failure Treatment 

James Januzzi, MD, Massachusetts General Hospital, Harvard Medical School

By Katherine H. Saunders, MD, DABOM, Co-Founder of Intellihealth and Clinical Assistant Professor of Medicine at Weill Cornell Medicine.

With the Food and Drug Administration’s recent approval of tirzepatide (Zepbound) for the treatment of obesity, we are poised to take a significant step forward in combatting the nation’s obesity epidemic. The question is, will we seize this opportunity to turn the 

Like semaglutide (of Ozempic and Wegovy fame), tirzepatide was originally developed as a treatment for type 2 diabetes (marketed under the Mounjaro brand), and it is what’s known as a GLP-1 agonist: it activates receptors for glucagon-like peptide-1, which stimulates insulin production and creates a feeling of fullness. But unlike semaglutide, tirzepatide also activates the receptors for a second nutrient-stimulated hormone, glucose-dependent insulinotropic polypeptide (GIP). This combination has proven highly effective, helping trial participants on the highest dose of tirzepatide lose an average of 22.5% of their body weight, compared to the highest dose of semaglutide’s average of about 15% in studies evaluating individuals with obesity and without type 2 diabetes.

The mere fact that these medications exist won’t be enough to overcome the obesity crisis. People need to actually 

 the treatment, and that will require broader change driven by the recognition that obesity is in fact a disease and not merely a lifestyle issue.

For most people with obesity, the standard advice to just eat less and exercise more doesn’t work. It’s not simply a matter of needing to try harder, or of balancing calories in versus calories out. The human body has evolved many mechanisms to actively resist weight loss. While some people are able to find success with lifestyle changes alone, obesity activates a range of physiological changes that make it extremely difficult for the vast majority of individuals with obesity to achieve clinically significant weight loss without medical guidance and, often, pharmacotherapy. Medications like Zepbound — used as part of a comprehensive, long-term weight management plan — can help override some of the hormonal, metabolic and neurobehavioral mechanisms preventing weight loss.

Major national and international health and medical organizations — including the World Health Organization, the American Medical Association, the American Heart Association, the American College of Surgeons, the Food and Drug Administration, and the National Institutes of Health — have acknowledged that obesity is a complex, chronic disease, but the U.S. health care industry continues to lag when it comes to putting that recognition into practice

Considering that 42% of American adults have obesity, medical schools devote remarkably little attention to the disease. As a result, many practitioners continue to maintain outdated ideas about obesity being simply a lifestyle issue, allowing stigma and weight bias to persist in healthcare settings. Many people with obesity avoid seeking care because of negative experiences with providers who rush to judgment. If we want to meet the magnitude of the obesity challenge, we’ll need to encourage more practitioners to treat obesity like the disease it is and spur more people with obesity to seek care.

Insurance coverage, or the lack thereof, also continues to reflect the stigma surrounding obesity. Although obesity is associated with more than 200 (expensive!) medical conditions such as heart disease, high blood pressure, type 2 diabetes, osteoarthritis, sleep apnea and certain types of cancer, many insurers and health plans don’t cover obesity treatment because they consider weight management to be nothing more than a “cosmetic” concern. Or they limit their coverage to nutrition counseling at one end of the spectrum or bariatric surgery at the other, ignoring the middle ground represented by comprehensive, evidence-based medical care.

Many health plans (most notably, Medicare) explicitly exclude coverage of medications for weight management. This needs to change if we want to extend the benefits of advances in the field of obesity medicine beyond the wealthy and those who already have serious weight-related complications. Now, with new medications and greater industry interest in conducting large-scale studies, we need to provide conclusive evidence to insurers that treating the underlying obesity is more cost-effective than trying to treat all the resulting complications separately. Yes, treating obesity is expensive, but 

 treating obesity is even more costly in terms of increased medical expenses, reduced economic productivity, and lost quality of life.

Because obesity has many causes and contributing factors that interact in complex ways, treatment needs to be highly personalized. Zepbound likely won’t be the best choice for everyone, but it provides individuals with the most effective anti-obesity agents yet — and others are on the way.

To make these innovations widely accessible, we need to let go of the idea that taking anti-obesity medications is somehow “cheating.” These new medications aren’t a magic bullet, and a healthy diet and physical activity will always be a critical part of any weight management plan. Let’s acknowledge that obesity is a chronic disease that requires medical care, and support those interested in exploring whether anti-obesity medications are right for them.

Editor's Note: This work reflects the views of the author and are not necessarily reflective of the publication or its owners.

Katherine H. Saunders, MD, DABOM, is the Co-Founder of Intellihealth (software and clinical services company democratizing access to medical obesity treatment), and Clinical Assistant Professor of Medicine at Weill Cornell Medicine

In this column, Katherine Saunders, MD, of Weill Cornell Medicine, provides perspective on the approval of tirzepatide for chronic weight management and what it might mean for patient access in the future. 

Will Tirzepatide Finally Turn the Tide in Access to Obesity Treatment?

Katherine Saunders, MD

Lung Cancer Biomarkers: A New Frontier in Early Detection with Lindsey Cotton, DO, DHSc, MS

Lung cancer remains the leading cause of cancer-related death in the United States, responsible for more than 127,000 deaths annually. Despite advancements in treatment, survival outcomes remain closely tied to the stage at diagnosis—making early detection a critical focus in public health. While current U.S. Preventive Services Task Force (USPSTF) recommendations endorse screening for only a handful of cancers—lung, breast, cervical, and colorectal—these organ-specific guidelines leave the majority of lethal cancers without structured early detection strategies.

Recent innovations in biomarker development have aimed to address this gap, using noninvasive methods such as blood, urine, saliva, or stool to detect cancer at early stages. Two major categories of these tools are emerging: organ-specific early detection tests and multi-cancer early detection tests (MCEDs), the latter offering the potential to identify multiple malignancies from a single blood sample. For lung cancer, both types of biomarkers are under active investigation, with ongoing efforts focused on improving accuracy, defining appropriate use populations, and addressing challenges related to cost, downstream testing, and insurance coverage.

Joining our host Albert Rizzo, MD, in this episode of Lungcast is clinician-scientist and expert in liquid biopsy development Lindsey Cotton, D.O.Med, DHSc, MS, chief medical officer of Cotton Medical Consultants. Cotton explores the evolving science of lung cancer biomarkers and their role in early detection and details the benefits and challenges of both organ-specific and multi-cancer tests.

“We need to move beyond this one size fits all screening recommendations. We need to take a more personalized approach looking at comprehensive risk assessment. I've been really fortunate to have a swarm of academic colleagues and peers as thought partners that are making so many incredible, groundbreaking movements in this area,” Cotton said. “I would also say it doesn't matter how great a test is. I want to emphasize the importance of implementation science in this field. Even the best test won't save lives if it isn't used, we don't have access, or it's not covered.”

Lungcast is a monthly respiratory news podcast series hosted by Albert Rizzo, MD, chief medical officer of the ALA, and produced by 

This episode of Lungcast features a discussion on emerging research in lung cancer biomarkers and early detection.

Lung Cancer Biomarkers: A New Frontier in Early Detection with Lindsey Cotton, DOMed, DHSc, MS

Lindsey Cotton, D.O.Med, DHSc, MS

The Future of Obesity Treatment with Martha Gulati, MD

 in Philadelphia, PA, Martha Gulati, MD, associate director of both Barbra Streisand Women’s Heart Center and the Preventive and Cardiac Rehabilitation Center at Smidt Heart Institute, presented her discussion on the challenges and advancements in the 

 has been well documented. Affecting millions of adults and children worldwide, it is associated with several adiposity-related complications, including hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, cancer, and cardiovascular disease.

Recent treatments, such as glucagon-like peptide-1 (GLP-1) receptor agonists and incretin therapies, have allowed for the medical treatment of obesity and other adiposity-related diseases. This, in turn, has led to a new degree of intervention surrounding the maintenance and treatment of its resulting complications.

Gulati praised recent studies and medications for highlighting the connection between obesity and a variety of life-threatening complications, indicating significant progress in the last few years.

“Obviously these medications started out as treatment for diabetes, and we’ve had that well established for a number of years,” Gulati told 

. “But the idea that we could use these medications for more than that, and particularly for obesity, was the first step, showing that they were effective at weight loss.”

Gulati also noted that the renewed focus on incretin therapies has also resulted in a much broader application for similar medications, potentially moving far beyond diabetes and obesity.

“We’ve looked at people with kidney dysfunction and we’ve seen the improvement in the kidney function,” Gulati said. “We’ve seen these drugs proven to be effective in reducing fibrosis of the liver, and so for our patients with MASH, that also gives us a therapy that we’ve really not had for that important disease, which was often advancing to both end stage liver disease and increased risk of liver cancer.”

In addition to a broader spectrum of treatable diseases, Gulati noted that incretin therapies are also capable of forestalling cardiovascular events by eliminating their precursors, such as sleep apnea.

“And for cardiac patients, I think that’s incredibly important because we know if you have obstructive sleep apnea, you’re putting yourself at a greater risk for heart disease of many different forms, including things like atrial fibrillation,” Gulati said. “So being able to stop these risk factors is a compelling clinical indication, and I think it has the potential to really change the effect that obesity has had on these rising rates.”

Gulati agrees with the pressing concern of figuring out how to consistently get these medications to patients in need; however, she also notes the comparative importance of focusing on prevention in addition to treatment.

“If we don’t keep focusing on prevention, we’re just going to continue the same way of treating advanced cardiovascular disease. Let’s keep putting in stents, let’s do ablations for atrial fibrillation, let’s do all these big expensive procedures because we aren’t able to provide these advanced therapies early enough,” Gulati told 

. “And I think that we have to change the medical paradigm of how we treat patients and how we think about prevention and how we invest in prevention at the forefront.”

Gulati also expressed excitement at the forward momentum of obesity studies, commenting on ongoing research and the drugs currently in the pipeline. She notes the necessity of expanding the mechanisms and methods of treatment in addition to new medications, in an effort to maintain cost-effectiveness and allow for the largest number of patients to receive care.

“And I think the other point is, can we change how we deliver it, too? And the reason that that’s important is not because it’s an injection, but it’s the reason these drugs have become so costly; they’re injectable, and they have to stay cool, and we have to deliver them in a mechanism that they built around it.”

Gulati reports the following disclosures: Boehringer Ingelheim Pharmaceuticals, Lilly, Medtronic, Merck & Co., New Amsterdam, Zoll, and others.

Gulati M. Obesity Management Role of Medical Management in CVD. Presented at the 9

 Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

Christensen S, Nelson C. Chronicity of obesity and the importance of early treatment to reduce cardiometabolic risk and improve body composition. Obes Pillars. 2025;15:100175. Published 2025 Apr 2. doi:10.1016/j.obpill.2025.100175

Gulati covers the promises and pitfalls of the healthcare world’s increasing focus on obesity as a disease and the variety of complications to which it gives rise.

Martha Gulati, MD

Unmet Needs in CSU Management

Video content above is prompted by the following:

What are the unmet needs in CSU management? How is the field evolving?

Chronic spontaneous urticaria (CSU) management faces several unmet needs, including the need for more effective treatments and better understanding of disease mechanisms. Current therapies often fail to provide complete symptom relief, and there is a significant demand for novel therapeutic options. The field is evolving with advancements in biologics and personalized medicine approaches, aiming to improve patient outcomes. Research is focusing on identifying biomarkers for better diagnosis and treatment stratification. Additionally, there is an emphasis on improving patient quality of life through comprehensive management strategies.

Panelists discuss the unmet needs in chronic spontaneous urticaria (CSU) management, highlighting the evolution of the field toward more personalized and effective treatment strategies to address refractory symptoms.

Naiem Issa, MD, PhD

The ALPACA trial demonstrated lepodisiran, a long-acting small interfering RNA therapy, significantly and durably reduces lipoprotein(a) [Lp(a)] levels, with effects lasting up to 18 months.

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, with Eli Lilly and Company announcing the therapy’s progression to the phase 3 ACCLAIM-Lp(a) trial.

“Nearly a quarter of the world’s population has elevated Lp(a), increasing cardiovascular risk, yet no approved therapies exist,” said Steve Nissen, MD, chief academic officer of the Heart Vascular & Thoracic Institute at the Cleveland Clinic. “These findings suggest siRNA approaches like lepodisiran could offer durable benefits with long-term dosing.”

Conducted across 66 sites on 5 continents, ALPACA randomized 320 patients with elevated Lp(a) to receive placebo or one of several lepodisiran regimens. The primary outcome of the trial was time-averaged percent change in Lp(a) from day 60 to 180. Results suggested patients receiving lepodisiran achieved reductions of 40.8%, 75.2%, and 93.9% for the 16 mg, 96 mg, and pooled 400 mg dose groups, respectively.

Additionally, those receiving 400 mg at baseline and day 180 maintained a 74.2% reduction in Lp(a). Secondary outcome analyses revealed the 400 mg group also experienced sustained reductions in apolipoprotein B, with decreases of 14.1% at day 60 and 13.7% at day 180.

Safety data showed treatment-emergent adverse events in 1% of placebo recipients, 3% of the 16 mg group, 12% of the 96 mg group, and 14% of the 400 mg group. No serious adverse events were linked to lepodisiran, though one death occurred in the 16 mg group due to chronic coronary disease complications.

For more on the trial and its implications, check out our interview with principal investigator Nissen.

Lepodisiran, ALPACA, and Lp(a), with Steve Nissen, MD

Relevant disclosures for AbbVie, Inc., Amgen, arrowhead, Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Encarda, Esperion Therapeutics, Medtronic, Mineralys, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics.

Nissen SE, Ni W, Shen X, et al. Lepodisiran — A Long-Duration Small Interfering RNA Targeting Lipoprotein(a). 

. Published online March 30, 2025. doi: 10.1056/nejmoa2415818

Eli Lilly and Company. Lilly’s lepodisiran reduced levels of genetically inherited heart disease risk factor, lipoprotein(a), by nearly 94% from baseline at the highest tested dose in adults with elevated levels | Eli Lilly and Company. Eli Lilly and Company. Published March 30, 2025. Accessed March 30, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lillys-lepodisiran-reduced-levels-genetically-inherited-heart

Steve Nissen, MD, discusses the phase 2 ALPACA trial and how it informs the potential of lepodisiran for lowering Lp(a). 

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