Bypass and Beyond

Redefining Roles and Mechanisms of Obesity Treatment at ENDO 2025

Endocrine News talks with the chair and presenters of “Bariatric Surgery and Emerging Medications: Redefining Roles and Mechanisms,”an ENDO 2025 session that analyzes a variety of factors that are impacted by bariatric surgery including postsurgical hypoglycemia, surgery versus pharmacological solutions, as well as a number of molecular mechanisms of the surgery itself.

With so many recent advances in our understanding of obesity and its treatment, ENDO 2025 is rightly spotlighting this topic. One session in particular, happening July 15th from 9:00 a.m. to 10:30 a.m., should have clinicians and researchers abuzz — “Bariatric Surgery and Emerging Medications: Redefining Roles and Mechanisms” explores both how bariatric surgery facilitates weight loss as well as how it is evolving in the context of novel anti-obesity medications.

The three presentations include a deep dive into the physiologic and molecular mechanisms underlying how bariatric surgery facilitates weight loss and improves metabolic health, an exploration of the various considerations regarding post-bariatric hypoglycemia, and a comparison of the safety and efficacy profiles of bariatric surgery and pharmacotherapy. Ultimately, attendees will gain tremendous insights into optimizing patient outcomes.

The session will be chaired by Marc J. Tetel, PhD, of the Neuroscience Department at Wellesley College, in Wellesley, Mass. Tetel, who started attending ENDO during his postdoc and has attended ever since, is an apt pick for the role. He credits ENDO itself with introducing him to molecular endocrinology. “ENDO quickly became a place where I could connect with colleagues and good friends every year and keep up with the most recent and important advances in hormone health and research. I look forward to this meeting every year as a chance to immerse myself in the latest hormone science breakthroughs and clinical advancements, as well as have a great time with friends.”

Although the session is not directly related to his specific research area, he views staying up to date on the most recent advances in obesity treatment and cutting-edge research as very important.

“I began in the obesity and metabolism field by investigating the effects of estrogens and the gut microbiome on metabolism in female mice,” he explains. “More recently, my lab has been exploring the effects of hormones and lifestyle choices on the interaction between the gut and vaginal microbiomes in women. My hope is that this session will result in clinical, translational, and basic researchers coming together to discuss these important topics, engage in discussions with each other, and generate new and exciting collaborations!”

Mechanisms of Bariatric Surgery 

Nadejda Bozadjieva-Kramer, PhD, assistant professor of surgery at the University of Michigan Medical School, in Ann Arbor, Mich. will talk about physiologic changes post-bariatric surgery. She became interested in this topic after seeing that bariatric surgery provides important metabolic benefits beyond weight reduction, including reversing such comorbidities as type 2 diabetes and cardiovascular complications. “Despite the potent incretin mimetic therapies for obesity available now, bariatric surgery remains the most sustainable approach for weight loss,” she explains. “We aimed to uncover a better understanding of the molecular mechanisms underlying the effects of bariatric surgery that lead to weight-independent benefits.”

Her research team has been particularly interested in how the intestine communicates with the liver following bariatric surgery. “Our data shows an improvement in liver fibrosis after sleeve gastrectomy that was not dependent on weight loss. We also found that interrupting gut-to-liver communication after sleeve gastrectomy can negatively impact liver metabolism and the maintenance of lean muscle mass. These studies have really highlighted an interest in exploring further how the intestine affects other systems during rapid weight loss,” she says.

“Our data shows an improvement in liver fibrosis after sleeve gastrectomy that was not dependent on weight loss. We also found that interrupting gut-to-liver communication after sleeve gastrectomy can negatively impact liver metabolism and the maintenance of lean muscle mass. These studies have really highlighted an interest in exploring further how the intestine affects other systems during rapid weight loss.” — Nadejda Bozadjieva-Kramer, PhD, assistant professor of surgery, University of Michigan Medical School, Ann Arbor, Mich.

A decade of research has supported the benefits bariatric surgery confers, and this has allowed additional advantages to emerge: “Along with this data, we can now also identify which procedure may be a better approach for a specific patient based on their comorbidities. All of these have really allowed us to optimize the health outcomes for our patients,” explains Kramer. It’s also true that many of the pharmacologic approaches used to treat obesity today have stemmed from research in bariatric surgery.

Even with so many wonderful advances occurring, one thing remains clear says Kramer: “We have great tools for addressing obesity, but it’s important to remember that they must be tailored for individual patients to achieve the best health outcomes.”

Post-Bariatric Hypoglycemia

Tricia M-M. Tan, MB ChB, FRCP, PhD, FRCPath, professor of metabolic medicine and endocrinology at the Imperial College London, in London, United Kingdom, will talk about the clinical features, diagnostic criteria, and pathophysiological mechanisms of post-bariatric hypoglycemia (PBH) in addition to evidence-based management strategies. Despite the many good outcomes associated with bariatric surgery, PBH does occur with most types, including Roux-en-Y gastric bypass, sleeve gastrectomy, and single-anastomosis gastric bypass (it is uncommon after gastric banding). It is also increasingly seen, given the uptick in these surgeries performed to manage obesity. All of this coupled with the impact that hypoglycemia can have on patient quality of life makes the need for understanding and treating this condition clear.

Tan, in fact, led the committee that developed the UK’s 2024 guidance on PBH on behalf of the UK Society for Endocrinology. She says her interest in the topic was aroused by the plight of patients with PBH. “The hypoglycemia is particularly intractable in many cases and is a very real disability. Our effort to develop guidance was spurred by the fact that this diagnosis was underrecognized and evidence-based treatment was lacking,” she explains.

The prevalence of PBH, she explains, depends on how PBH is defined. Hypoglycemia severe enough to warrant hospital admission is about 1 in 100 to 1,000. However, surveys of people who have had bariatric surgery suggest that about one in three have symptoms consistent with hypoglycemia. Indeed, if PBH is defined according to provocative tests (e.g., glucose tolerance tests) it may be as common as one in three to one in five. If using continuous glucose monitoring (CGM) criteria, Tan’s and other groups’ research has shown that significant hypoglycemia occurs in as many as one in four to three in four. “However the vast majority of such patients are asymptomatic, and we know that bariatric surgery is overall beneficial to health, so it is questionable whether CGM-defined hypoglycemia constitutes a problem,” she explains.

“My lab has been exploring the effects of hormones and lifestyle choices on the interaction between the gut and vaginal microbiomes in women. My hope is that this session will result in clinical, translational, and basic researchers coming together to discuss these important topics, engage in discussions with each other, and generate new and exciting collaborations!” —  Marc J. Tetel, PhD, Neuroscience Department, Wellesley College, Wellesley, Mass.

In “Society for Endocrinology guidelines for the diagnosis and management of post-bariatric hypoglycaemia,” published in Endocrine Connections, Tan and team recommend what she calls a “pragmatic” definition of PBH that is biochemically confirmed (<3.0 mmol/L [54 mg/dL]), demonstrates typical hypoglycemic symptoms (Whipple triad), and includes investigation and exclusion of alternative causes.

Which patients are at higher risk of developing PBH or of having worse associated outcomes is as yet unclear. Tan says some studies have shown associations with certain attributes (e.g., people who have higher HbA1c pre-surgery, who are younger, who are female, and who lose higher degrees of weight), whereas others have not. Unfortunately, this uncertainty makes preventing PBH a particular challenge. However, theories do exist about what mechanism(s) underly its development.

Tan explains: “Post-bariatric patients generally exhibit rapid absorption of food (either because gastric emptying is accelerated, or because the food bypasses the stomach and is routed to the jejunum). This leads to the development of a large glucose spike, which leads to sharp increases in incretin hormone (GLP-1 particularly) and insulin secretion — hence disposal of the glucose.”

Although in many patients, this leads to improved glucose tolerance and therefore improvements in diabetes, if present, in some, it causes “overswing hypoglycemia.” Other theories include impaired suppression of basal insulin secretion in response to hypoglycemia and excessive meal-stimulated insulin secretion; defective alpha-cell secretion of glucagon; alterations in bile acid kinetics, which may in turn trigger excess FGF-19 secretion; release of inflammatory cytokines such as IL-1beta; and, more recently, increased gut serotonin secretion. “Whether all these mechanisms are operative in all PBH patients, or perhaps that different patients have different dominant mechanisms is not as yet clear,” says Tan.

For management, Tan again cites the 2024 evidence-based UK guidelines. They advocate for a combination of dietary modification (e.g., reducing carbohydrate content in meals, eating small amounts often), patient education, avoidance of fluids near mealtimes, use of pharmacotherapy (e.g., acarbose and somatostatin analogues) in selected cases, and consideration of surgical approaches (e.g., gastrostomy feeding or reversal of surgery).

The takeaway for clinicians, explains Tan is threefold. “First and foremost, it’s important to recognize and diagnose PBH in our patients who have had bariatric surgery. Secondly, for many people with PBH, a sensible dietary approach goes a very long way to ameliorating it. Thirdly, don’t underestimate the contribution of psychology to this condition: support from our psychology colleagues can be extremely helpful in promoting resilience and self-management skills.”

“First and foremost, it’s important to recognize and diagnose PBH in our patients who have had bariatric surgery. Secondly, for many people with PBH, a sensible dietary approach goes a very long way to ameliorating it. Thirdly, don’t underestimate the contribution of psychology to this condition: support from our psychology colleagues can be extremely helpful in promoting resilience and self-management skills.” — Tricia M-M. Tan, MB ChB, FRCP, PhD, FRCPath, professor of metabolic medicine and endocrinology, Imperial College London, London, U.K.

Although Tan’s presentation topic is primarily based around post-bariatric surgery, she is no stranger to the pharmacologic side of obesity treatment, nor, for that matter, to ENDO, which she has been attending since 2003. In fact, she presented research from “Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study” at ENDO 2018. “We showed that this co-infusion was practical and safe and improved their glucose control and their weight. This research cemented the concept of ‘multi-agonism’ of incretin receptors for treatment of diabetes and obesity, and this is now a practical reality for our patients with the advent of tirzepatide and the multi-agonists that are in the offing,” she says.

Outcomes of Bariatric Surgery Compared to Anti-Obesity Medications

Nasreen Alfaris, MD, MPH, of the King Fahad Medical City, in Riyadh, Saudi Arabia, will connect all of the dots in her comparison of the surgical and pharmacologic approaches to obesity management. She, too, has been a regular ENDO attendee over the years, calling it it a cornerstone in her professional calendar. “ENDO is more than just a scientific conference,” she says, “it’s a gathering of leading experts in endocrinology from around the world, offering a dynamic space to exchange knowledge, explore the latest advances in the field, and engage in meaningful collaboration.” She describes ENDO and other leading conferences as “platforms that have allowed me to share insights, engage with global experts, and contribute to the ongoing advancement of obesity medicine.”

Alfariswas drawn to obesity work byrecognizing the rapidly increasing burden of obesity as a chronic disease. “Despite its impact as a major driver of numerous health conditions and premature death,” she says, “there remains a scarcity of healthcare professionals who specialize in its management. Recognizing this gap, I chose to dedicate my career to obesity medicine — to contribute meaningfully to the care of individuals living with obesity and to help address this pressing public health challenge through evidence-based treatment and advocacy. The factors driving obesity are complex and multifaceted, and we are working diligently to combat this epidemic.” She very recently served on the commission that developed the“Definition and Diagnostic Criteria of Clinical Obesity,” published in January in The Lancet Diabetes and Endocrinology.

Echoing some of the themes Kramer and Tan mention, Alfaris says, “treatment decisions should be personalized, based on factors such as disease severity, associated complications, patient preferences, previous treatment history, and access to therapy. Obesity is a chronic, progressive, relapsing, and heterogeneous disease, and we are fortunate to live in a time where there are multiple safe and effective treatment options available.”

Like Kramer, she points to the long-term data supporting the efficacy of metabolic surgery, for durable weight loss as well as improvements in other conditions (e.g., type 2 diabetes, non-alcoholic fatty liver disease, polycystic ovary syndrome, and obstructive sleep apnea). “With the advent of newer pharmacologic agents, we are now seeing impressive outcomes in terms of weight loss and additional metabolic and health benefits beyond weight loss. These medications are transforming the way we approach obesity management. Therefore, the question should not be framed as ‘drugs versus surgery,’ but rather how we can use a combination of therapies to best address the needs of each individual patient,” she explains.

“As clinicians, we should be prepared to utilize the full range of medical and surgical tools available to us — particularly pharmacotherapy and metabolic surgery — and tailor treatment strategies based on the individual patient’s disease severity, complications, and treatment response. Optimal care requires a personalized approach; there is no one-size-fits-all approach to obesity management.” — Nasreen Alfaris, MD, MPH, King Fahad Medical City, Riyadh, Saudi Arabia

Alfaris says we must focus on ensuring better access to care for individuals living with obesity — particularly those with health-impairing forms of the disease. “That is why, in the ‘Definition and Diagnostic Criteria of Clinical Obesity,’ we worked to develop a more nuanced, disease-based classification system. This framework recognizes both clinical and pre-clinical obesity, with the goal of improving access to treatment for individuals with significant metabolic, mechanical, or psychological consequences of obesity — regardless of body mass index (BMI). This shift moves us away from a simplistic, BMI-driven model and toward a more equitable and medically appropriate approach to obesity care.” In addition, this approach should leverage all available evidence-based interventions to achieve the best possible outcomes for patients.

“As clinicians,” says Alfaris, “we should be prepared to utilize the full range of medical and surgical tools available to us — particularly pharmacotherapy and metabolic surgery — and tailor treatment strategies based on the individual patient’s disease severity, complications, and treatment response. Optimal care requires a personalized approach; there is no one-size-fits-all approach to obesity management.”

Horvath is a freelance writer based in Baltimore, Md. In the May issue, she wrote about recent studies that presented new insights into osteoporosis and bone health.