A Relentless Pursuit: JES Invites Collaborative Obesity Research

Three editors of the Journal of the Endocrine Society (JES) recently published an editorial titled “From Fundamentals to the Clinic: Advancing Obesity Research in Endocrinology,” recognizing that the landscape of obesity research has rapidly evolved in the past five years, and that sharing scientific data is an important step toward addressing the growing global obesity epidemic.

Zeynep Madak-Erdogan, PhD, associate professor of nutrition in the Department of Food Science and Human Nutrition at the University of Illinois Urbana-Champaign in Urbana, Ill., and editor-in-chief of JES; Stephen Hammes, MD, PhD, the Louis S. Wolk Distinguished Professor of Medicine, chief of the Division of Endocrinology, Diabetes and Metabolism, and executive vice-chair of the Department of Medicine at the University of Rochester in Rochester, N.Y., president of the Endocrine Society and deputy editor of JES; and M. Furkan Burak, MD, instructor in Medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, and associate editor of JES, write that they’re issuing “a strong call to action for the scientific and medical communities to pursue the boundaries of obesity research and treatment relentlessly.”

“The obesity epidemic is not going away any time soon, so continued research that allows us to better understand the pathophysiology of weight gain will undoubtably lead to better health care options for everybody,” Hammes says. “This editorial is key for the Endocrine Society, as it re-iterates our commitment to obesity research, and emphasizes the important leadership role that we hope the Journal of the Endocrine Society can take in this important field.”

Endocrine News caught up with Madak-Erdogan and Burak to discuss the editorial, the current dynamic landscape in obesity research, and what they would like to see over the course of the next five years.

Endocrine News: First off, tell me a little about the origins of this editorial. What made you want to sit down and write it?

Zeynep Madak-Erdogan: We were inspired by the rising prevalence of obesity and obesity-related issues, current health trends, and increasing research and clinical attention to new drugs that target obesity. With our new associate editor for obesity, Dr. Furkan Burak, joining our team, it was the right time to write this editorial.

M. Furkan Burak: Seventy to 75%  of the entire U.S. is either overweight or obese, and it’s basically out of control; it has become a new normal. The treatment of obesity has been problematic for more than a hundred years, with lots of medications withdrawn,  patients and providers changing their perceptions, and a lack of specialists. Then there is all the stigma. Obesity is unfortunately stigmatized, and this has created a lot of problems.

It’s time to increase awareness, reverse all the mistakes and the bad reputation of obesity treatment, and show people that this is a chronic disease like other chronic diseases. Because of recent developments that have given us more tools, this is the time to go full-force. We must increase the awareness of patients, the public, governments, industry, academia, everyone, to address this worldwide problem.

EN: You point out that obesity intersects with economic burdens and social disparities. Can you speak a little more to those disparities and why addressing them is crucial to addressing obesity as a whole?

ZME: Obesity and related health concerns disproportionately affect underserved populations. This condition often leads to increased medical expenses due to associated health conditions like diabetes, heart disease, and cancer. While new drugs offer hope, their high costs restrict access significantly. Additionally, there are ongoing issues with access to nutritious food, safe places to exercise, preventive healthcare, and targeted education programs, all of which are essential for mitigating the disparate negative impacts of obesity.

Research is very valuable, and the best research comes from collaborations. We need to collaborate all around the world, put the resources into it, bring the previous data in, and create new data in a collaborative way. Sharing the resources really makes an impact.

M. Furkan Burak, MD, instructor in Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Ma.; associate editor, JES

MFB: Obesity comes as a package. Obesity leads to diabetes; it’s very hard to treat diabetes patients because many have lower socioeconomical status. They cannot get the best tools for chronic disease management, and this only makes things worse. How they live, how they eat, how they treat the disease are all becoming more and more problematic, so we need to address that first, create equity and teach them. It’s not easy to address this, but at the end of the day, this costs the world trillions of dollars. It takes a big portion of the world GDP, if you think about all of obesity and its related problems. I think it’s critical to address and  treat obesity in everyone who wants treatment, and to create tools to reach out and improve the disparities so treatment is available to everyone.

EN: Can you speak a little more to the dynamic and changing landscape of obesity research?

ZME: Very exciting developments are happening in this field. Obesity research is rapidly evolving, incorporating advances in molecular mechanisms, the gut microbiome, and pharmacology to develop personalized treatments. There’s also a growing focus on the psychological and behavioral factors contributing to obesity, alongside the use of personal devices and wearables in monitoring and managing health. Additionally, interdisciplinary approaches and public health policies are being explored to create environments that support healthier lifestyle choices on a community-wide scale.

MFB: The FDA has approved anti-obesity medications before, but they were very limited, although commonly prescribed. For example, phentermine is an amphetamine substitute. It was approved in 1959, and was the most commonly prescribed anti-obesity medication until recently. But this medication increases blood pressure, increases the oxygen requirement of the heart, increases anxiety and arrhythmia risk, all things that can be very problematic in obesity patients. It is not ideal, and you can use it for, at most, one year. And in a chronic disease, you then regain the weight, and then you get discouraged, and all the stigmatization continues, so you just give up. Gain, lose, gain. This weight cycling is much more problematic than even having obesity.

We started to understand what is really changing in obesity, in adipose tissue, in the heart, in the vasculature, in the brain. And knowing the biology really helped us, so we understood what is missing or changing. We are replacing what is missing; we are mimicking the body’s own mechanism with biological treatments of obesity. We have started getting huge success, almost to the surgical level of weight loss.

For example, I have patients [on GLP-1 agonists] losing 30% of total body weight, which is like a surgical weight loss, while treating their heart attacks, while treating their diabetes, while treating their asthma, obstructive sleep apnea, and chronic kidney disease. Now, we are at the stage of the optimal treatment paradigm, which we didn’t have for hundreds of years. Because if you understand the biology, you can treat the disease.

That’s why the landscape is dynamic— it’s changing from problematic, repurposed drugs to really targeted drugs, biological drugs that address obesity as a whole, rather than just causing weight loss—an approach that creates all kinds of other problems.

EN: What has caused this recent surge in obesity research in the past five years?

ZME: We can list several factors. Of course, there is the rising global prevalence of obesity, new drugs being approved and developed, and innovations in technology, which allow for more detailed data analysis and new treatment methods. There is also Increased public awareness, and there are more opportunities for interdisciplinary collaboration, as well as enhanced public and private funding, in this space. They have significantly contributed to this surge.

EN: You also point out the recent popularity of drugs like Ozempic, as well as many other digital health tools to augment diet and exercise. In your opinion, are there any therapies you’re most excited about? Any you’re still wary of?

ZME: Several drugs are in the clinical pipeline that have dual/triple activities towards GLP-1 and other clinically relevant targets, such as retatrutide, survodutide etc. Oral GLP-1 RAs like orforglipron are also very exciting.  

This is a very exciting time for individuals with obesity as well as for the scientific community. With a recently-added curated collection of high-quality obesity articles, online at JES – open access, as are all JES articles — we are keeping an eye on new developments and opportunities.

Zeynep Madak-Erdogan, PhD, associate professor of nutrition, Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign in Urbana, Ill.; editor-in-chief, JES

EN: On that note, how can we make sure these medications and therapies are available to anyone who needs them?

ZME: The new research findings are very important. Hopefully, new research will inform policy around limiting out-of-pocket costs to improve affordability, negotiating fair prices for coverage by Medicare and Medicaid, and potential patent reform to address high drug prices due to incremental innovation.

MFB: Data works. I think everybody wants to know that this is a cost-effective treatment, and this is really helping the people. It’s not just a cosmetic problem, so you lose your weight, then you feel great. It’s more than that. The outcome trials are producing more data, and because we are scientists, we are physicians, we go by the data. I think the cardiovascular outcome trials have shown such huge success that even insurance companies have started understanding this.

For example, I am on the Masshealth Drug Utilization Review board; it’s very progressive. It’s federal insurance, but they’re really thinking about how we can help people, and what is  the new science, and what should we do? And they are thinking about cost-effectiveness. Masshealth started covering these anti-obesity drugs, including Wegovy.

It’s time to increase awareness, reverse all the mistakes and the bad reputation of obesity treatment, and show people that this is a chronic disease like other chronic diseases. Because of recent developments that have given us more tools, this is the time to go full-force. We must increase the awareness of patients, the public, governments, industry, academia, everyone, to address this worldwide problem.

M. Furkan Burak, MD, instructor in Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Ma.; associate editor, JES

I think insurance companies understand that this is a cost-effective treatment. If somebody doesn’t have a heart attack, doesn’t get CKD, doesn’t get sleep apnea, feels better, does not lose their job, feels lighter, and does not have diabetes, and none of the complications happen, it’s very cost-effective. We are more and more understanding this, which will likely make the coverage increase. We are not there yet, but we are happy about the pace of understanding from the payer’s standpoint.

EN: As obesity research continues to expand, what is your ideal landscape in this field over the next five years?

ZME: I can mention two things: Increased funding not only from private sector but also from the NIH, and improved access to new therapies.

MFB: One unmet need is muscle mass preservation, so I really want to see muscle preserving agents in the market, and then all these other lifestyle modifications focusing on muscle mass preservation might be better utilized.

Second, we have patients with a BMI of 50, 60, 70, more, and 15% weight loss is not enough. We have more drugs coming down the pipeline that we are excited about, other GI peptides, and there may be synergistic and additive effects. I am thinking of amylin, GIP, GLP, glucagon. And all these gastrointestinal peptide combinations are showing that you can normalize the liver fat, help NASH, and achieve 25% to 30% of total body weight loss in some individuals.

EN: Finally, what’s the main thing you hope readers take away from your editorial and this piece?

ZME: This is a very exciting time for individuals with obesity as well as for the scientific community. With a recently-added curated collection of high-quality obesity articles, online at JES – open access, as are all JES articles — we are keeping an eye on new developments and opportunities. We encourage submissions from prospective authors, including research articles, technical resources, reviews, and clinical studies to be considered for publication. Our areas of publishing interest include Genetic Associations, Hormones Related to Obesity, Obesity Disparities, Obesity-related Conditions, Pediatrics and Obstetrics, Therapies, Environmental Factors, and Diabetes.

Obesity research is rapidly evolving, incorporating advances in molecular mechanisms, the gut microbiome, and pharmacology to develop personalized treatments. There’s also a growing focus on the psychological and behavioral factors contributing to obesity, alongside the use of personal devices and wearables in monitoring and managing health. Additionally, interdisciplinary approaches and public health policies are being explored to create environments that support healthier lifestyle choices on a community-wide scale.

Zeynep Madak-Erdogan, PhD, associate professor of nutrition, Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign in Urbana, Ill.; editor-in-chief, JES

MFB: Research is very valuable, and the best research comes from collaborations. We need to collaborate all around the world, put the resources into it, bring the previous data in, and create new data in a collaborative way. Sharing the resources really makes an impact.

It’s a huge patient population; different market segments are tempting for different companies. They should be very cautious about drug development discipline and principles. All the basic science and translational work has to be of the highest quality. You cannot just do simple experiments, pick up something from a genetic screen, and go straight to humans. That would create very flawed obesity research again.

If we see horror stories, if we see bad side effects, that will also discourage patients, or even the scientific community. We need to be cautious in both drug development and obesity research, and never leave the basic principles behind just because there’s a race to bring something to the clinic.  We should be thinking about those principles–do not harm, first–and be cautious in terms of translation from animal to humans. But at the same time, go full force, collaborate, and fight obesity from different angles.