In this episode of Private Practice Perspectives, Dr. Naresh Gunaratnam, current president and board chair of Digestive Health Physician Association, speaks with Dr. Larry Kim, current president of AGA, about how GI societies can best support fellows and early career physicians.

In this episode of Private Practice Perspectives, Dr. Naresh Gunaratnam, current president and board chair of Digestive Health Physician Association, speaks with Dr. Larry Kim, current president of AGA, about how GI societies can best support fellows and early career physicians.

In this episode of Private Practice Perspectives, Dr. Naresh Gunaratnam, current president and board chair of Digestive Health Physician Association, speaks with Dr. Larry Kim, current president of AGA, about how GI societies can best support fellows and early career physicians.

On Nov. 22, 2014, 8 years after he came back from Iraq with “crippling” posttraumatic stress disorder (PTSD), Jonathan Lubecky took his first dose of the psychedelic compound methylenedioxymethamphetamine (MDMA). Lubecky, a Marine, Army, and National Guard veteran, described his path to MDMA therapy in in the New Horizons in Health podcast.

After 5 suicide attempts and “the hundreds of times I thought about it or stood on a bridge or had a plan,” he felt he had run out of options. Then, in a counseling session, a psychiatric intern slid a piece of paper across the table to him. It read “Google MDMA PTSD.”

Luckily for Lubecky, a space in a clinical trial opened up, in which he had 8 hours of talk therapy with specially trained therapists, combined with MDMA. “MDMA is a tool that opens up the mind, body and spirit,” he said, “so you can heal and process all those memories and traumas that are causing yourissues. It puts you in a middle place where you can talk about trauma without having panic attacks, without your body betraying you, and look at it from a different perspective.” said he added, “It’s like doing therapy while being hugged by everyone who loves you in a bathtub full of puppies licking your face.” In 2023, 9 years after that first dose, Lubecky said, “I’ve been PTSD free longer than I had it.”

And now, in 2025, the research into psychedelic therapy for veterans like Lubecky is taking another step forward according to a report by Military.com. Nine VA facilities, in the Bronx, Los Angeles, Omaha, Palo Alto, Portland (Oregon), San Diego, San Francisco, West Haven, and White River Junction, are participating in long-term studies to test the safety and clinical impact of psychedelic compounds for PTSD, treatment-resistant depression, and anxiety disorders. 

Early trials from Johns Hopkins University, the Multidisciplinary Association for Psychedelic Studies (MAPS), and others found significant symptom reductions for some participants with chronic PTSD. MAPP2, the multisite phase 3 study that extended the findings of MAPP1, found that MDMA-assisted therapy significantly improved PTSD symptoms and functional impairment, compared with placebo-assisted therapy. Notably, of the 52 participants (including 16 veterans) 45 (86%) achieved a clinically meaningful benefit, and 37 (71%) no longer met criteria for PTSD by study end. Despite the promising findings, a US Food and Drug Administration (FDA) advisory panel recommended against approving the treatment.

In 2024 the VA issued a request for applications for proposals from its network of VA researchers and academic institutions to gather “definitive scientific evidence” on the potential efficacy and safety of psychedelic compounds, such as MDMA and psilocybin, when used in conjunction with psychotherapy. It would be the first time since the 1960s that the VA had funded research on such compounds. 

Funding proposals for such research have cycled in and out of Congress for years, but have gathered more steam in the last few years. The 2024 National Defense Authorization Act directed the US Department of Defense to establish a process for funding clinical research into the use of certain psychedelic substances to treat PTSD and traumatic brain injury. In April 2024, Representatives Lou Correa (D-CA) and Jack Bergman (R-MI), cochairs of the Psychedelics Advancing Therapies (PATH) caucus, introduced the Innovative Therapies Centers of Excellence Act of 2025, bipartisan legislation that would increase federally funded research on innovative therapies to treat veterans with PTSD, substance use disorder, and depression. It would also, if enacted, direct the VA to create ≥ 5 dedicated centers of excellence to study the therapeutic uses of psychedelic substances. The bill has also been endorsed by the American Legion, Veterans of Foreign Wars, Iraq and Afghanistan Veterans of America, Disabled American Veterans, and the Wounded Warrior Project.

The current administration has two strong high-level supporters of psychedelics research: VA Secretary Doug Collins and US Department of Health and Human Service Secretary Robert F. Kennedy Jr. Sec. Kennedy has castigated the FDA for what he calls “aggressive suppression” of alternative and complementary treatments, including psychedelics. This, although the FDA granted breakthrough therapy status for MDMA for treating PTSD and psilocybin for treating depression in 2018 and 2019, respectively, as well a pivotal draft guidance in 2023 for the development of psychedelic drugs for psychiatric disorders, substance use disorders, and various medical conditions.

Collins, citing an “eye-opening” discussion with Kennedy, enthusiastically backs the research into psychedelics. In a May 2025 hearing that was mainly a series of testy exchanges about his proposed budget slashing, he emphasized the importance of keeping and expanding VA programs and studies on psychedelic treatments, something he has been advocating for since the beginning of his appointment. “We want to make sure we’re not closing off any outlet for a veteran who could be helped by these programs,” he said. 

Taking the intern’s advice to look into MDMA, Jonathan Lubecky said, was one of the best decisions he’d ever made. But “it’s not the MDMA that fixes you,” he said. “It’s the therapy. It’s the therapist working with you and you doing the hard work.”

On Nov. 22, 2014, 8 years after he came back from Iraq with “crippling” posttraumatic stress disorder (PTSD), Jonathan Lubecky took his first dose of the psychedelic compound methylenedioxymethamphetamine (MDMA). Lubecky, a Marine, Army, and National Guard veteran, described his path to MDMA therapy in in the New Horizons in Health podcast.

After 5 suicide attempts and “the hundreds of times I thought about it or stood on a bridge or had a plan,” he felt he had run out of options. Then, in a counseling session, a psychiatric intern slid a piece of paper across the table to him. It read “Google MDMA PTSD.”

Luckily for Lubecky, a space in a clinical trial opened up, in which he had 8 hours of talk therapy with specially trained therapists, combined with MDMA. “MDMA is a tool that opens up the mind, body and spirit,” he said, “so you can heal and process all those memories and traumas that are causing yourissues. It puts you in a middle place where you can talk about trauma without having panic attacks, without your body betraying you, and look at it from a different perspective.” said he added, “It’s like doing therapy while being hugged by everyone who loves you in a bathtub full of puppies licking your face.” In 2023, 9 years after that first dose, Lubecky said, “I’ve been PTSD free longer than I had it.”

And now, in 2025, the research into psychedelic therapy for veterans like Lubecky is taking another step forward according to a report by Military.com. Nine VA facilities, in the Bronx, Los Angeles, Omaha, Palo Alto, Portland (Oregon), San Diego, San Francisco, West Haven, and White River Junction, are participating in long-term studies to test the safety and clinical impact of psychedelic compounds for PTSD, treatment-resistant depression, and anxiety disorders. 

Early trials from Johns Hopkins University, the Multidisciplinary Association for Psychedelic Studies (MAPS), and others found significant symptom reductions for some participants with chronic PTSD. MAPP2, the multisite phase 3 study that extended the findings of MAPP1, found that MDMA-assisted therapy significantly improved PTSD symptoms and functional impairment, compared with placebo-assisted therapy. Notably, of the 52 participants (including 16 veterans) 45 (86%) achieved a clinically meaningful benefit, and 37 (71%) no longer met criteria for PTSD by study end. Despite the promising findings, a US Food and Drug Administration (FDA) advisory panel recommended against approving the treatment.

In 2024 the VA issued a request for applications for proposals from its network of VA researchers and academic institutions to gather “definitive scientific evidence” on the potential efficacy and safety of psychedelic compounds, such as MDMA and psilocybin, when used in conjunction with psychotherapy. It would be the first time since the 1960s that the VA had funded research on such compounds. 

Funding proposals for such research have cycled in and out of Congress for years, but have gathered more steam in the last few years. The 2024 National Defense Authorization Act directed the US Department of Defense to establish a process for funding clinical research into the use of certain psychedelic substances to treat PTSD and traumatic brain injury. In April 2024, Representatives Lou Correa (D-CA) and Jack Bergman (R-MI), cochairs of the Psychedelics Advancing Therapies (PATH) caucus, introduced the Innovative Therapies Centers of Excellence Act of 2025, bipartisan legislation that would increase federally funded research on innovative therapies to treat veterans with PTSD, substance use disorder, and depression. It would also, if enacted, direct the VA to create ≥ 5 dedicated centers of excellence to study the therapeutic uses of psychedelic substances. The bill has also been endorsed by the American Legion, Veterans of Foreign Wars, Iraq and Afghanistan Veterans of America, Disabled American Veterans, and the Wounded Warrior Project.

The current administration has two strong high-level supporters of psychedelics research: VA Secretary Doug Collins and US Department of Health and Human Service Secretary Robert F. Kennedy Jr. Sec. Kennedy has castigated the FDA for what he calls “aggressive suppression” of alternative and complementary treatments, including psychedelics. This, although the FDA granted breakthrough therapy status for MDMA for treating PTSD and psilocybin for treating depression in 2018 and 2019, respectively, as well a pivotal draft guidance in 2023 for the development of psychedelic drugs for psychiatric disorders, substance use disorders, and various medical conditions.

Collins, citing an “eye-opening” discussion with Kennedy, enthusiastically backs the research into psychedelics. In a May 2025 hearing that was mainly a series of testy exchanges about his proposed budget slashing, he emphasized the importance of keeping and expanding VA programs and studies on psychedelic treatments, something he has been advocating for since the beginning of his appointment. “We want to make sure we’re not closing off any outlet for a veteran who could be helped by these programs,” he said. 

Taking the intern’s advice to look into MDMA, Jonathan Lubecky said, was one of the best decisions he’d ever made. But “it’s not the MDMA that fixes you,” he said. “It’s the therapy. It’s the therapist working with you and you doing the hard work.”

On Nov. 22, 2014, 8 years after he came back from Iraq with “crippling” posttraumatic stress disorder (PTSD), Jonathan Lubecky took his first dose of the psychedelic compound methylenedioxymethamphetamine (MDMA). Lubecky, a Marine, Army, and National Guard veteran, described his path to MDMA therapy in in the New Horizons in Health podcast.

After 5 suicide attempts and “the hundreds of times I thought about it or stood on a bridge or had a plan,” he felt he had run out of options. Then, in a counseling session, a psychiatric intern slid a piece of paper across the table to him. It read “Google MDMA PTSD.”

Luckily for Lubecky, a space in a clinical trial opened up, in which he had 8 hours of talk therapy with specially trained therapists, combined with MDMA. “MDMA is a tool that opens up the mind, body and spirit,” he said, “so you can heal and process all those memories and traumas that are causing yourissues. It puts you in a middle place where you can talk about trauma without having panic attacks, without your body betraying you, and look at it from a different perspective.” said he added, “It’s like doing therapy while being hugged by everyone who loves you in a bathtub full of puppies licking your face.” In 2023, 9 years after that first dose, Lubecky said, “I’ve been PTSD free longer than I had it.”

And now, in 2025, the research into psychedelic therapy for veterans like Lubecky is taking another step forward according to a report by Military.com. Nine VA facilities, in the Bronx, Los Angeles, Omaha, Palo Alto, Portland (Oregon), San Diego, San Francisco, West Haven, and White River Junction, are participating in long-term studies to test the safety and clinical impact of psychedelic compounds for PTSD, treatment-resistant depression, and anxiety disorders. 

Early trials from Johns Hopkins University, the Multidisciplinary Association for Psychedelic Studies (MAPS), and others found significant symptom reductions for some participants with chronic PTSD. MAPP2, the multisite phase 3 study that extended the findings of MAPP1, found that MDMA-assisted therapy significantly improved PTSD symptoms and functional impairment, compared with placebo-assisted therapy. Notably, of the 52 participants (including 16 veterans) 45 (86%) achieved a clinically meaningful benefit, and 37 (71%) no longer met criteria for PTSD by study end. Despite the promising findings, a US Food and Drug Administration (FDA) advisory panel recommended against approving the treatment.

In 2024 the VA issued a request for applications for proposals from its network of VA researchers and academic institutions to gather “definitive scientific evidence” on the potential efficacy and safety of psychedelic compounds, such as MDMA and psilocybin, when used in conjunction with psychotherapy. It would be the first time since the 1960s that the VA had funded research on such compounds. 

Funding proposals for such research have cycled in and out of Congress for years, but have gathered more steam in the last few years. The 2024 National Defense Authorization Act directed the US Department of Defense to establish a process for funding clinical research into the use of certain psychedelic substances to treat PTSD and traumatic brain injury. In April 2024, Representatives Lou Correa (D-CA) and Jack Bergman (R-MI), cochairs of the Psychedelics Advancing Therapies (PATH) caucus, introduced the Innovative Therapies Centers of Excellence Act of 2025, bipartisan legislation that would increase federally funded research on innovative therapies to treat veterans with PTSD, substance use disorder, and depression. It would also, if enacted, direct the VA to create ≥ 5 dedicated centers of excellence to study the therapeutic uses of psychedelic substances. The bill has also been endorsed by the American Legion, Veterans of Foreign Wars, Iraq and Afghanistan Veterans of America, Disabled American Veterans, and the Wounded Warrior Project.

The current administration has two strong high-level supporters of psychedelics research: VA Secretary Doug Collins and US Department of Health and Human Service Secretary Robert F. Kennedy Jr. Sec. Kennedy has castigated the FDA for what he calls “aggressive suppression” of alternative and complementary treatments, including psychedelics. This, although the FDA granted breakthrough therapy status for MDMA for treating PTSD and psilocybin for treating depression in 2018 and 2019, respectively, as well a pivotal draft guidance in 2023 for the development of psychedelic drugs for psychiatric disorders, substance use disorders, and various medical conditions.

Collins, citing an “eye-opening” discussion with Kennedy, enthusiastically backs the research into psychedelics. In a May 2025 hearing that was mainly a series of testy exchanges about his proposed budget slashing, he emphasized the importance of keeping and expanding VA programs and studies on psychedelic treatments, something he has been advocating for since the beginning of his appointment. “We want to make sure we’re not closing off any outlet for a veteran who could be helped by these programs,” he said. 

Taking the intern’s advice to look into MDMA, Jonathan Lubecky said, was one of the best decisions he’d ever made. But “it’s not the MDMA that fixes you,” he said. “It’s the therapy. It’s the therapist working with you and you doing the hard work.”

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

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

PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

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

PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

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

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

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

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

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

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

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

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

Military medical personnel rely on individual critical tasks lists (ICTLs) to maintain proficiency in essential medical skills during deployments. However, sustaining these competencies in a low-casualty operational setting presents unique challenges. Traditional training methods, such as lectures or simulations outside operational contexts, may lack engagement and fail to replicate the stressors of real-world scenarios. Previous research has emphasized the importance of continuous medical readiness training in austere environments, highlighting the need for innovative approaches.^1,2

The Litter Olympics was developed as an in-theater training exercise designed to enhance medical readiness, foster interdisciplinary teamwork, and incorporate physical exertion into skill maintenance. By requiring teams to carry a patient litter through multiple “events,” the exercise reinforced teamwork within a medical readiness-focused series inspired by an Olympic decathlon. This article discusses the feasibility, effectiveness, and potential impact of the Litter Olympics as a training tool for maintaining ICTLs in a deployed environment.

Program

The Litter Olympics were implemented at a Role 3 medical facility in Baghdad, Iraq, where teams composed of individuals from military occupational specialties (MOSs) and areas of concentration (AOCs) participated. Role 3 facilities provide specialty surgical and critical care capabilities, enabling a robust medical training environment.³ The event was designed to reflect the interdisciplinary nature of deployed medical teams and incorporated hands-on training stations covering critical medical skills such as traction splinting, spinal precautions, patient movement, hemorrhage control, airway management, and tactical evacuation procedures.

Tasks were selected based on their relevance to deployed medical care and their inclusion in ICTLs, ensuring alignment with mission-essential skills. Participants were evaluated on task completion, efficiency, and teamwork by experienced medical personnel. Postexercise surveys assessed skill improvement, confidence levels, and areas for refinement. Future studies should incorporate structured performance metrics, such as pre- and postevent evaluations, to quantify proficiency gains (Table 1).

Five mixed MOS/AOC teams participated in the event, completing the exercise in an average time of 50 minutes (Table 2). Participants reported increased confidence in performing ICTs, particularly in patient movement, hemorrhage control, and airway management. The interdisciplinary nature of the teams facilitated peer teaching and cross-training, allowing individuals to better understand each other’s roles and responsibilities. This mirrors findings in previous studies on predeployment training that emphasize the importance of collaborative, hands-on learning.⁴ The physical aspect of the exercise was well received, as it simulated operational conditions and reinforced endurance in high-stress environments. Some tasks, such as cricothyroidotomy and satellite radio setup, required additional instruction, highlighting areas for improvement in future iterations.

Discussion

The Litter Olympics provide a dynamic alternative to traditional classroom instruction by integrating realistic, scenario-based training. However, several limitations were identified. The most significant was the lack of formalized outcome metrics. While qualitative feedback was overwhelmingly positive, no structured performance assessment tool, such as pre- and postevent skill evaluations, was used. Future studies should incorporate objective measures of competency to strengthen the evidence base for this training model. Additionally, participant feedback suggested that more structured debriefing sessions postexercise would enhance learning retention and provide actionable insights for future program modifications.

Another consideration is the scalability and adaptability of the exercise. While effective in a Role 3 setting, modifications may be required for smaller units or lower levels of care. Future iterations could adapt the format for Role 1 or 2 environments by reducing the number of stations while preserving the core training elements. Furthermore, the event relied on access to specialized personnel and equipment, which may not always be feasible in austere settings. Developing a streamlined version focusing on essential tasks could improve accessibility and sustainability across different operational environments.

Participants expressed a preference for this hands-on, competitive training model over traditional didactic instruction. However, further research should compare skill retention rates between the Litter Olympics and other training modalities to validate effectiveness. While peer teaching was a notable strength of the event, structured mentorship from senior medical personnel could further enhance skill acquisition and reinforce best practices.

Conclusions

The Litter Olympics present a reproducible, engaging, and effective method for sustaining medical readiness in a deployed Role 3 setting. By fostering interdisciplinary collaboration and incorporating physical and cognitive stressors, it enhances both individual and team preparedness. Future research should develop standardized, measurable outcome assessments, explore application in diverse deployment settings, and optimize scalability for broader military medical training programs. Standardized evaluation tools should be developed to quantify performance improvements, and the training model should be expanded to include lower levels of care and nonmedical personnel. Structured debriefing sessions would also provide valuable insight into lessons learned and potential refinements. By integrating these enhancements, the Litter Olympics can serve as a cornerstone for maintaining operational medical readiness in deployed environments.

Military medical personnel rely on individual critical tasks lists (ICTLs) to maintain proficiency in essential medical skills during deployments. However, sustaining these competencies in a low-casualty operational setting presents unique challenges. Traditional training methods, such as lectures or simulations outside operational contexts, may lack engagement and fail to replicate the stressors of real-world scenarios. Previous research has emphasized the importance of continuous medical readiness training in austere environments, highlighting the need for innovative approaches.^1,2

The Litter Olympics was developed as an in-theater training exercise designed to enhance medical readiness, foster interdisciplinary teamwork, and incorporate physical exertion into skill maintenance. By requiring teams to carry a patient litter through multiple “events,” the exercise reinforced teamwork within a medical readiness-focused series inspired by an Olympic decathlon. This article discusses the feasibility, effectiveness, and potential impact of the Litter Olympics as a training tool for maintaining ICTLs in a deployed environment.

Program

The Litter Olympics were implemented at a Role 3 medical facility in Baghdad, Iraq, where teams composed of individuals from military occupational specialties (MOSs) and areas of concentration (AOCs) participated. Role 3 facilities provide specialty surgical and critical care capabilities, enabling a robust medical training environment.³ The event was designed to reflect the interdisciplinary nature of deployed medical teams and incorporated hands-on training stations covering critical medical skills such as traction splinting, spinal precautions, patient movement, hemorrhage control, airway management, and tactical evacuation procedures.

Tasks were selected based on their relevance to deployed medical care and their inclusion in ICTLs, ensuring alignment with mission-essential skills. Participants were evaluated on task completion, efficiency, and teamwork by experienced medical personnel. Postexercise surveys assessed skill improvement, confidence levels, and areas for refinement. Future studies should incorporate structured performance metrics, such as pre- and postevent evaluations, to quantify proficiency gains (Table 1).

Five mixed MOS/AOC teams participated in the event, completing the exercise in an average time of 50 minutes (Table 2). Participants reported increased confidence in performing ICTs, particularly in patient movement, hemorrhage control, and airway management. The interdisciplinary nature of the teams facilitated peer teaching and cross-training, allowing individuals to better understand each other’s roles and responsibilities. This mirrors findings in previous studies on predeployment training that emphasize the importance of collaborative, hands-on learning.⁴ The physical aspect of the exercise was well received, as it simulated operational conditions and reinforced endurance in high-stress environments. Some tasks, such as cricothyroidotomy and satellite radio setup, required additional instruction, highlighting areas for improvement in future iterations.

Discussion

The Litter Olympics provide a dynamic alternative to traditional classroom instruction by integrating realistic, scenario-based training. However, several limitations were identified. The most significant was the lack of formalized outcome metrics. While qualitative feedback was overwhelmingly positive, no structured performance assessment tool, such as pre- and postevent skill evaluations, was used. Future studies should incorporate objective measures of competency to strengthen the evidence base for this training model. Additionally, participant feedback suggested that more structured debriefing sessions postexercise would enhance learning retention and provide actionable insights for future program modifications.

Another consideration is the scalability and adaptability of the exercise. While effective in a Role 3 setting, modifications may be required for smaller units or lower levels of care. Future iterations could adapt the format for Role 1 or 2 environments by reducing the number of stations while preserving the core training elements. Furthermore, the event relied on access to specialized personnel and equipment, which may not always be feasible in austere settings. Developing a streamlined version focusing on essential tasks could improve accessibility and sustainability across different operational environments.

Participants expressed a preference for this hands-on, competitive training model over traditional didactic instruction. However, further research should compare skill retention rates between the Litter Olympics and other training modalities to validate effectiveness. While peer teaching was a notable strength of the event, structured mentorship from senior medical personnel could further enhance skill acquisition and reinforce best practices.

Conclusions

The Litter Olympics present a reproducible, engaging, and effective method for sustaining medical readiness in a deployed Role 3 setting. By fostering interdisciplinary collaboration and incorporating physical and cognitive stressors, it enhances both individual and team preparedness. Future research should develop standardized, measurable outcome assessments, explore application in diverse deployment settings, and optimize scalability for broader military medical training programs. Standardized evaluation tools should be developed to quantify performance improvements, and the training model should be expanded to include lower levels of care and nonmedical personnel. Structured debriefing sessions would also provide valuable insight into lessons learned and potential refinements. By integrating these enhancements, the Litter Olympics can serve as a cornerstone for maintaining operational medical readiness in deployed environments.

Military medical personnel rely on individual critical tasks lists (ICTLs) to maintain proficiency in essential medical skills during deployments. However, sustaining these competencies in a low-casualty operational setting presents unique challenges. Traditional training methods, such as lectures or simulations outside operational contexts, may lack engagement and fail to replicate the stressors of real-world scenarios. Previous research has emphasized the importance of continuous medical readiness training in austere environments, highlighting the need for innovative approaches.^1,2

The Litter Olympics was developed as an in-theater training exercise designed to enhance medical readiness, foster interdisciplinary teamwork, and incorporate physical exertion into skill maintenance. By requiring teams to carry a patient litter through multiple “events,” the exercise reinforced teamwork within a medical readiness-focused series inspired by an Olympic decathlon. This article discusses the feasibility, effectiveness, and potential impact of the Litter Olympics as a training tool for maintaining ICTLs in a deployed environment.

Program

The Litter Olympics were implemented at a Role 3 medical facility in Baghdad, Iraq, where teams composed of individuals from military occupational specialties (MOSs) and areas of concentration (AOCs) participated. Role 3 facilities provide specialty surgical and critical care capabilities, enabling a robust medical training environment.³ The event was designed to reflect the interdisciplinary nature of deployed medical teams and incorporated hands-on training stations covering critical medical skills such as traction splinting, spinal precautions, patient movement, hemorrhage control, airway management, and tactical evacuation procedures.

Tasks were selected based on their relevance to deployed medical care and their inclusion in ICTLs, ensuring alignment with mission-essential skills. Participants were evaluated on task completion, efficiency, and teamwork by experienced medical personnel. Postexercise surveys assessed skill improvement, confidence levels, and areas for refinement. Future studies should incorporate structured performance metrics, such as pre- and postevent evaluations, to quantify proficiency gains (Table 1).

Five mixed MOS/AOC teams participated in the event, completing the exercise in an average time of 50 minutes (Table 2). Participants reported increased confidence in performing ICTs, particularly in patient movement, hemorrhage control, and airway management. The interdisciplinary nature of the teams facilitated peer teaching and cross-training, allowing individuals to better understand each other’s roles and responsibilities. This mirrors findings in previous studies on predeployment training that emphasize the importance of collaborative, hands-on learning.⁴ The physical aspect of the exercise was well received, as it simulated operational conditions and reinforced endurance in high-stress environments. Some tasks, such as cricothyroidotomy and satellite radio setup, required additional instruction, highlighting areas for improvement in future iterations.

Discussion

The Litter Olympics provide a dynamic alternative to traditional classroom instruction by integrating realistic, scenario-based training. However, several limitations were identified. The most significant was the lack of formalized outcome metrics. While qualitative feedback was overwhelmingly positive, no structured performance assessment tool, such as pre- and postevent skill evaluations, was used. Future studies should incorporate objective measures of competency to strengthen the evidence base for this training model. Additionally, participant feedback suggested that more structured debriefing sessions postexercise would enhance learning retention and provide actionable insights for future program modifications.

Another consideration is the scalability and adaptability of the exercise. While effective in a Role 3 setting, modifications may be required for smaller units or lower levels of care. Future iterations could adapt the format for Role 1 or 2 environments by reducing the number of stations while preserving the core training elements. Furthermore, the event relied on access to specialized personnel and equipment, which may not always be feasible in austere settings. Developing a streamlined version focusing on essential tasks could improve accessibility and sustainability across different operational environments.

Participants expressed a preference for this hands-on, competitive training model over traditional didactic instruction. However, further research should compare skill retention rates between the Litter Olympics and other training modalities to validate effectiveness. While peer teaching was a notable strength of the event, structured mentorship from senior medical personnel could further enhance skill acquisition and reinforce best practices.

Conclusions

The Litter Olympics present a reproducible, engaging, and effective method for sustaining medical readiness in a deployed Role 3 setting. By fostering interdisciplinary collaboration and incorporating physical and cognitive stressors, it enhances both individual and team preparedness. Future research should develop standardized, measurable outcome assessments, explore application in diverse deployment settings, and optimize scalability for broader military medical training programs. Standardized evaluation tools should be developed to quantify performance improvements, and the training model should be expanded to include lower levels of care and nonmedical personnel. Structured debriefing sessions would also provide valuable insight into lessons learned and potential refinements. By integrating these enhancements, the Litter Olympics can serve as a cornerstone for maintaining operational medical readiness in deployed environments.

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com . 

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com . 

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com .