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Capsule sponge-based surveillance could be used in lieu of endoscopy for low-risk Barrett’s esophagus (BE) surveillance, a prospective multisite UK study found. The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy. 

Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet. 

“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.

Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.

In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”

The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.

“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.

The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.

 

Study Details

Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.

Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.

In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.

The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group. 

The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.

Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”

“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”

Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”

Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”

One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”

This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health. 

Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.

A version of this article appeared on Medscape.com.

Capsule sponge-based surveillance could be used in lieu of endoscopy for low-risk Barrett’s esophagus (BE) surveillance, a prospective multisite UK study found. The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy. 

Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet. 

“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.

Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.

In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”

The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.

“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.

The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.

 

Study Details

Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.

Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.

In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.

The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group. 

The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.

Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”

“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”

Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”

Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”

One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”

This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health. 

Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.

A version of this article appeared on Medscape.com.

Capsule sponge-based surveillance could be used in lieu of endoscopy for low-risk Barrett’s esophagus (BE) surveillance, a prospective multisite UK study found. The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy. 

Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet. 

“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.

Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.

In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”

The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.

“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.

The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.

 

Study Details

Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.

Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.

In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.

The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group. 

The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.

Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”

“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”

Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”

Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”

One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”

This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health. 

Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Emerging research indicates that phenotype-based testing may help identify which biologic process is driving an individual’s obesity, enabling clinicians to better tailor antiobesity medication (AOM) to the patient.

Currently, patient response to AOMs varies widely, with some patients responding robustly to AOMs and others responding weakly or not at all.

For example, trials of the GLP-1 semaglutide found that 32%-39.6% of people are “super responders,” achieving weight loss in excess of 20%, and a subgroup of 10.2%-16.7% of individuals are nonresponders. Similar variability was found with other AOMs, including the GLP-1 liraglutide and tirzepatide, a dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist.

Studies of semaglutide suggest that people with obesity and type 2 diabetes (T2D) lose less weight on the drug than those without T2D, and men tend to lose less weight than women.

However, little else is known about predictors of response rates for various AOMs, and medication selection is typically based on patient or physician preference, comorbidities, medication interactions, and insurance coverage.

Although definitions of a “nonresponder” vary, the Endocrine Society’s latest guideline, which many clinicians follow, states that an AOM is considered effective if patients lose more than 5% of their body weight within 3 months.

Can nonresponders and lower responders be identified and helped? Yes, but it’s complicated.

“Treating obesity effectively means recognizing that not all patients respond the same way to the same treatment, and that’s not a failure; it’s a signal,” said Andres Acosta, MD, PhD, an obesity expert at Mayo Clinic, Rochester, Minnesota, and a cofounder of Phenomix Sciences, a biotech company in Menlo Park, California.

“Obesity is not a single disease. It’s a complex, multifactorial condition driven by diverse biological pathways,” he told GI & Hepatology News. “Semaglutide and other GLP-1s primarily act by reducing appetite and slowing gastric emptying, but not all patients have obesity that is primarily driven by appetite dysregulation.”

 

Phenotype-Based Profiling

Figuring out what drives an individual’s obesity is where a phenotype-based profiling test could possibly help.

Acosta and colleagues previously used a variety of validated studies and questionnaires to identify four phenotypes that represent distinct biologic drivers of obesity: hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In their pragmatic clinical trial, phenotype-guided AOM selection was associated with 1.75-fold greater weight loss after 12 months than the standard approach to drug selection, with mean weight loss of 15.9% and 9%, respectively.

“If a patient’s obesity isn’t primarily rooted in the mechanisms targeted by a particular drug, their response will naturally be limited,” Acosta said. “It’s not that they’re failing the medication; the medication simply isn’t the right match for their biology.”

For their new study, published online in Cell Metabolism, Acosta and colleagues built on their previous research by analyzing the genetic and nongenetic factors that influenced calories needed to reach satiation (Calories to Satiation [CTS]) in adults with obesity. They then used machine learning techniques to develop a CTS gene risk score (CTS-GRS) that could be measured by a DNA saliva test.

The study included 717 adults with obesity (mean age, 41; 75% women) with marked variability in satiation, ranging from 140 to 2166 kcals to reach satiation.

CTS was assessed through an ad libitum meal, combined with physiological and behavioral evaluations, including calorimetry, imaging, blood sampling, and gastric emptying tests. The largest contributors to CTS variability were sex and genetic factors, while other anthropometric measurements played lesser roles.

Various analyses and assessments of participants’ CTS-GRS scores showed that individuals with a high CTS-GRS, or hungry brain phenotype, experienced significantly greater weight loss when treated with phentermine/topiramate than those with a low CTS-GRS, or hungry gut, phenotype. After 52 weeks of treatment, individuals with the hungry brain phenotype lost an average of 17.4% of their body weight compared with 11.2% in those with the hungry gut phenotype.

An analysis of a separate 16-week study showed that patients with the hungry gut phenotype responded better to the GLP-1 liraglutide, losing 6.4% total body weight, compared to 3.3% for those with the hungry brain phenotype.

Overall, the CTS-GRS test predicted drug response with up to 84% accuracy (area under the curve, 0.76 in men and 0.84 in women). The authors acknowledged that these results need to be replicated prospectively and in more diverse populations to validate the test’s predictive ability.

“This kind of phenotype-based profiling allows us to predict which patients are more likely to respond and who might need a different intervention,” Acosta said. “It’s a critical step toward eliminating trial-and-error in obesity treatment.”

The test (MyPhenome test) is used at more than 80 healthcare clinics in the United States, according to Phenomix Sciences, which manufactures it. A company spokesperson said the test does not require FDA approval because it is used to predict obesity phenotypes to help inform treatment, but not to identify specific medications or other interventions. “If it were to do the latter,” the spokesperson said, “it would be considered a ‘companion diagnostic’ and subject to the FDA clearance process.”

 

What to Do if an AOM Isn’t Working?

It’s one thing to predict whether an individual might do better on one drug vs another, but what should clinicians do meanwhile to optimize weight loss for their patients who may be struggling on a particular drug?

“Efforts to predict the response to GLP-1 therapy have been a hot topic,” noted Sriram Machineni, MD, associate professor at Montefiore Medical Center, Bronx, New York, and founding director of the Fleischer Institute Medical Weight Center at Montefiore Einstein. Although the current study showed that genetic testing could predict responders, like Acosta, he agreed that the results need to be replicated in a prospective manner.

“In the absence of a validated tool for predicting response to specific medications, we use a prioritization process for trialing medications,” Machineni told GI & Hepatology News. “The prioritization is based on the suitability of the side-effect profile to the specific patient, including contraindications; benefits independent of weight loss, such as cardiovascular protection for semaglutide; average efficacy; and financial accessibility for patients.”

Predicting responders isn’t straightforward, said Robert Kushner, MD, professor of medicine and medical education at the Feinberg School of Medicine at Northwestern University and medical director of the Wellness Institute at Northwestern Memorial Hospital in Chicago.

“Despite looking at baseline demographic data such as race, ethnicity, age, weight, and BMI, we are unable to predict who will lose more or less weight,” he told GI & Hepatology News. The one exception is that women generally lose more weight than men. “However, even among females, we cannot discern which females will lose more weight than other females,” he said.

If an individual is not showing sufficient weight loss on a particular medication, “we first explore potential reasons that can be addressed, such as the patient is not taking the medication or is skipping doses,” Kushner said. If need be, they discuss changing to a different drug to improve compliance. He also stresses the importance of making lifestyle changes in diet and physical activity for patients taking AOMs.

Often patients who do not lose at least 5% of their weight within 3 months are not likely to respond well to that medication even if they remain on it. “So, early response rates determine longer-term success,” Kushner said.

Acosta said that if a patient isn’t responding to one class of medication, he pivots to a treatment better aligned with their phenotype. “That could mean switching from a GLP-1 to a medication like [naltrexone/bupropion] or trying a new method altogether,” he said. “The key is that the treatment decision is rooted in the patient’s biology, not just a reaction to short-term results. We also emphasize the importance of long-term follow-up and support.”

The goal isn’t just weight loss but also improved health and quality of life, Acosta said. “Whether through medication, surgery, or behavior change, what matters most is tailoring the care plan to each individual’s unique biology and needs.”

The new study received support from the Mayo Clinic Clinical Research Trials Unit, Vivus Inc., and Phenomix Sciences. Acosta is supported by a National Institutes of Health grant.

Acosta is a co-founder and inventor of intellectual property licensed to Phenomix Sciences Inc.; has served as a consultant for Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Boehringer Ingelheim, Currax Pharmaceuticals, Nestlé, Bausch Health, and Rare Diseases; and has received research support or had contracts with Vivus Inc., Satiogen Pharmaceuticals, Boehringer Ingelheim, and Rhythm Pharmaceuticals. Machineni has been involved in semaglutide and tirzepatide clinical trials and has been a consultant to Novo Nordisk, Eli Lilly and Company, and Rhythm Pharmaceuticals. Kushner is on the scientific advisory board for Novo Nordisk.

A version of this article appeared on Medscape.com.

Emerging research indicates that phenotype-based testing may help identify which biologic process is driving an individual’s obesity, enabling clinicians to better tailor antiobesity medication (AOM) to the patient.

Currently, patient response to AOMs varies widely, with some patients responding robustly to AOMs and others responding weakly or not at all.

For example, trials of the GLP-1 semaglutide found that 32%-39.6% of people are “super responders,” achieving weight loss in excess of 20%, and a subgroup of 10.2%-16.7% of individuals are nonresponders. Similar variability was found with other AOMs, including the GLP-1 liraglutide and tirzepatide, a dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist.

Studies of semaglutide suggest that people with obesity and type 2 diabetes (T2D) lose less weight on the drug than those without T2D, and men tend to lose less weight than women.

However, little else is known about predictors of response rates for various AOMs, and medication selection is typically based on patient or physician preference, comorbidities, medication interactions, and insurance coverage.

Although definitions of a “nonresponder” vary, the Endocrine Society’s latest guideline, which many clinicians follow, states that an AOM is considered effective if patients lose more than 5% of their body weight within 3 months.

Can nonresponders and lower responders be identified and helped? Yes, but it’s complicated.

“Treating obesity effectively means recognizing that not all patients respond the same way to the same treatment, and that’s not a failure; it’s a signal,” said Andres Acosta, MD, PhD, an obesity expert at Mayo Clinic, Rochester, Minnesota, and a cofounder of Phenomix Sciences, a biotech company in Menlo Park, California.

“Obesity is not a single disease. It’s a complex, multifactorial condition driven by diverse biological pathways,” he told GI & Hepatology News. “Semaglutide and other GLP-1s primarily act by reducing appetite and slowing gastric emptying, but not all patients have obesity that is primarily driven by appetite dysregulation.”

 

Phenotype-Based Profiling

Figuring out what drives an individual’s obesity is where a phenotype-based profiling test could possibly help.

Acosta and colleagues previously used a variety of validated studies and questionnaires to identify four phenotypes that represent distinct biologic drivers of obesity: hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In their pragmatic clinical trial, phenotype-guided AOM selection was associated with 1.75-fold greater weight loss after 12 months than the standard approach to drug selection, with mean weight loss of 15.9% and 9%, respectively.

“If a patient’s obesity isn’t primarily rooted in the mechanisms targeted by a particular drug, their response will naturally be limited,” Acosta said. “It’s not that they’re failing the medication; the medication simply isn’t the right match for their biology.”

For their new study, published online in Cell Metabolism, Acosta and colleagues built on their previous research by analyzing the genetic and nongenetic factors that influenced calories needed to reach satiation (Calories to Satiation [CTS]) in adults with obesity. They then used machine learning techniques to develop a CTS gene risk score (CTS-GRS) that could be measured by a DNA saliva test.

The study included 717 adults with obesity (mean age, 41; 75% women) with marked variability in satiation, ranging from 140 to 2166 kcals to reach satiation.

CTS was assessed through an ad libitum meal, combined with physiological and behavioral evaluations, including calorimetry, imaging, blood sampling, and gastric emptying tests. The largest contributors to CTS variability were sex and genetic factors, while other anthropometric measurements played lesser roles.

Various analyses and assessments of participants’ CTS-GRS scores showed that individuals with a high CTS-GRS, or hungry brain phenotype, experienced significantly greater weight loss when treated with phentermine/topiramate than those with a low CTS-GRS, or hungry gut, phenotype. After 52 weeks of treatment, individuals with the hungry brain phenotype lost an average of 17.4% of their body weight compared with 11.2% in those with the hungry gut phenotype.

An analysis of a separate 16-week study showed that patients with the hungry gut phenotype responded better to the GLP-1 liraglutide, losing 6.4% total body weight, compared to 3.3% for those with the hungry brain phenotype.

Overall, the CTS-GRS test predicted drug response with up to 84% accuracy (area under the curve, 0.76 in men and 0.84 in women). The authors acknowledged that these results need to be replicated prospectively and in more diverse populations to validate the test’s predictive ability.

“This kind of phenotype-based profiling allows us to predict which patients are more likely to respond and who might need a different intervention,” Acosta said. “It’s a critical step toward eliminating trial-and-error in obesity treatment.”

The test (MyPhenome test) is used at more than 80 healthcare clinics in the United States, according to Phenomix Sciences, which manufactures it. A company spokesperson said the test does not require FDA approval because it is used to predict obesity phenotypes to help inform treatment, but not to identify specific medications or other interventions. “If it were to do the latter,” the spokesperson said, “it would be considered a ‘companion diagnostic’ and subject to the FDA clearance process.”

 

What to Do if an AOM Isn’t Working?

It’s one thing to predict whether an individual might do better on one drug vs another, but what should clinicians do meanwhile to optimize weight loss for their patients who may be struggling on a particular drug?

“Efforts to predict the response to GLP-1 therapy have been a hot topic,” noted Sriram Machineni, MD, associate professor at Montefiore Medical Center, Bronx, New York, and founding director of the Fleischer Institute Medical Weight Center at Montefiore Einstein. Although the current study showed that genetic testing could predict responders, like Acosta, he agreed that the results need to be replicated in a prospective manner.

“In the absence of a validated tool for predicting response to specific medications, we use a prioritization process for trialing medications,” Machineni told GI & Hepatology News. “The prioritization is based on the suitability of the side-effect profile to the specific patient, including contraindications; benefits independent of weight loss, such as cardiovascular protection for semaglutide; average efficacy; and financial accessibility for patients.”

Predicting responders isn’t straightforward, said Robert Kushner, MD, professor of medicine and medical education at the Feinberg School of Medicine at Northwestern University and medical director of the Wellness Institute at Northwestern Memorial Hospital in Chicago.

“Despite looking at baseline demographic data such as race, ethnicity, age, weight, and BMI, we are unable to predict who will lose more or less weight,” he told GI & Hepatology News. The one exception is that women generally lose more weight than men. “However, even among females, we cannot discern which females will lose more weight than other females,” he said.

If an individual is not showing sufficient weight loss on a particular medication, “we first explore potential reasons that can be addressed, such as the patient is not taking the medication or is skipping doses,” Kushner said. If need be, they discuss changing to a different drug to improve compliance. He also stresses the importance of making lifestyle changes in diet and physical activity for patients taking AOMs.

Often patients who do not lose at least 5% of their weight within 3 months are not likely to respond well to that medication even if they remain on it. “So, early response rates determine longer-term success,” Kushner said.

Acosta said that if a patient isn’t responding to one class of medication, he pivots to a treatment better aligned with their phenotype. “That could mean switching from a GLP-1 to a medication like [naltrexone/bupropion] or trying a new method altogether,” he said. “The key is that the treatment decision is rooted in the patient’s biology, not just a reaction to short-term results. We also emphasize the importance of long-term follow-up and support.”

The goal isn’t just weight loss but also improved health and quality of life, Acosta said. “Whether through medication, surgery, or behavior change, what matters most is tailoring the care plan to each individual’s unique biology and needs.”

The new study received support from the Mayo Clinic Clinical Research Trials Unit, Vivus Inc., and Phenomix Sciences. Acosta is supported by a National Institutes of Health grant.

Acosta is a co-founder and inventor of intellectual property licensed to Phenomix Sciences Inc.; has served as a consultant for Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Boehringer Ingelheim, Currax Pharmaceuticals, Nestlé, Bausch Health, and Rare Diseases; and has received research support or had contracts with Vivus Inc., Satiogen Pharmaceuticals, Boehringer Ingelheim, and Rhythm Pharmaceuticals. Machineni has been involved in semaglutide and tirzepatide clinical trials and has been a consultant to Novo Nordisk, Eli Lilly and Company, and Rhythm Pharmaceuticals. Kushner is on the scientific advisory board for Novo Nordisk.

A version of this article appeared on Medscape.com.

Emerging research indicates that phenotype-based testing may help identify which biologic process is driving an individual’s obesity, enabling clinicians to better tailor antiobesity medication (AOM) to the patient.

Currently, patient response to AOMs varies widely, with some patients responding robustly to AOMs and others responding weakly or not at all.

For example, trials of the GLP-1 semaglutide found that 32%-39.6% of people are “super responders,” achieving weight loss in excess of 20%, and a subgroup of 10.2%-16.7% of individuals are nonresponders. Similar variability was found with other AOMs, including the GLP-1 liraglutide and tirzepatide, a dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist.

Studies of semaglutide suggest that people with obesity and type 2 diabetes (T2D) lose less weight on the drug than those without T2D, and men tend to lose less weight than women.

However, little else is known about predictors of response rates for various AOMs, and medication selection is typically based on patient or physician preference, comorbidities, medication interactions, and insurance coverage.

Although definitions of a “nonresponder” vary, the Endocrine Society’s latest guideline, which many clinicians follow, states that an AOM is considered effective if patients lose more than 5% of their body weight within 3 months.

Can nonresponders and lower responders be identified and helped? Yes, but it’s complicated.

“Treating obesity effectively means recognizing that not all patients respond the same way to the same treatment, and that’s not a failure; it’s a signal,” said Andres Acosta, MD, PhD, an obesity expert at Mayo Clinic, Rochester, Minnesota, and a cofounder of Phenomix Sciences, a biotech company in Menlo Park, California.

“Obesity is not a single disease. It’s a complex, multifactorial condition driven by diverse biological pathways,” he told GI & Hepatology News. “Semaglutide and other GLP-1s primarily act by reducing appetite and slowing gastric emptying, but not all patients have obesity that is primarily driven by appetite dysregulation.”

 

Phenotype-Based Profiling

Figuring out what drives an individual’s obesity is where a phenotype-based profiling test could possibly help.

Acosta and colleagues previously used a variety of validated studies and questionnaires to identify four phenotypes that represent distinct biologic drivers of obesity: hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In their pragmatic clinical trial, phenotype-guided AOM selection was associated with 1.75-fold greater weight loss after 12 months than the standard approach to drug selection, with mean weight loss of 15.9% and 9%, respectively.

“If a patient’s obesity isn’t primarily rooted in the mechanisms targeted by a particular drug, their response will naturally be limited,” Acosta said. “It’s not that they’re failing the medication; the medication simply isn’t the right match for their biology.”

For their new study, published online in Cell Metabolism, Acosta and colleagues built on their previous research by analyzing the genetic and nongenetic factors that influenced calories needed to reach satiation (Calories to Satiation [CTS]) in adults with obesity. They then used machine learning techniques to develop a CTS gene risk score (CTS-GRS) that could be measured by a DNA saliva test.

The study included 717 adults with obesity (mean age, 41; 75% women) with marked variability in satiation, ranging from 140 to 2166 kcals to reach satiation.

CTS was assessed through an ad libitum meal, combined with physiological and behavioral evaluations, including calorimetry, imaging, blood sampling, and gastric emptying tests. The largest contributors to CTS variability were sex and genetic factors, while other anthropometric measurements played lesser roles.

Various analyses and assessments of participants’ CTS-GRS scores showed that individuals with a high CTS-GRS, or hungry brain phenotype, experienced significantly greater weight loss when treated with phentermine/topiramate than those with a low CTS-GRS, or hungry gut, phenotype. After 52 weeks of treatment, individuals with the hungry brain phenotype lost an average of 17.4% of their body weight compared with 11.2% in those with the hungry gut phenotype.

An analysis of a separate 16-week study showed that patients with the hungry gut phenotype responded better to the GLP-1 liraglutide, losing 6.4% total body weight, compared to 3.3% for those with the hungry brain phenotype.

Overall, the CTS-GRS test predicted drug response with up to 84% accuracy (area under the curve, 0.76 in men and 0.84 in women). The authors acknowledged that these results need to be replicated prospectively and in more diverse populations to validate the test’s predictive ability.

“This kind of phenotype-based profiling allows us to predict which patients are more likely to respond and who might need a different intervention,” Acosta said. “It’s a critical step toward eliminating trial-and-error in obesity treatment.”

The test (MyPhenome test) is used at more than 80 healthcare clinics in the United States, according to Phenomix Sciences, which manufactures it. A company spokesperson said the test does not require FDA approval because it is used to predict obesity phenotypes to help inform treatment, but not to identify specific medications or other interventions. “If it were to do the latter,” the spokesperson said, “it would be considered a ‘companion diagnostic’ and subject to the FDA clearance process.”

 

What to Do if an AOM Isn’t Working?

It’s one thing to predict whether an individual might do better on one drug vs another, but what should clinicians do meanwhile to optimize weight loss for their patients who may be struggling on a particular drug?

“Efforts to predict the response to GLP-1 therapy have been a hot topic,” noted Sriram Machineni, MD, associate professor at Montefiore Medical Center, Bronx, New York, and founding director of the Fleischer Institute Medical Weight Center at Montefiore Einstein. Although the current study showed that genetic testing could predict responders, like Acosta, he agreed that the results need to be replicated in a prospective manner.

“In the absence of a validated tool for predicting response to specific medications, we use a prioritization process for trialing medications,” Machineni told GI & Hepatology News. “The prioritization is based on the suitability of the side-effect profile to the specific patient, including contraindications; benefits independent of weight loss, such as cardiovascular protection for semaglutide; average efficacy; and financial accessibility for patients.”

Predicting responders isn’t straightforward, said Robert Kushner, MD, professor of medicine and medical education at the Feinberg School of Medicine at Northwestern University and medical director of the Wellness Institute at Northwestern Memorial Hospital in Chicago.

“Despite looking at baseline demographic data such as race, ethnicity, age, weight, and BMI, we are unable to predict who will lose more or less weight,” he told GI & Hepatology News. The one exception is that women generally lose more weight than men. “However, even among females, we cannot discern which females will lose more weight than other females,” he said.

If an individual is not showing sufficient weight loss on a particular medication, “we first explore potential reasons that can be addressed, such as the patient is not taking the medication or is skipping doses,” Kushner said. If need be, they discuss changing to a different drug to improve compliance. He also stresses the importance of making lifestyle changes in diet and physical activity for patients taking AOMs.

Often patients who do not lose at least 5% of their weight within 3 months are not likely to respond well to that medication even if they remain on it. “So, early response rates determine longer-term success,” Kushner said.

Acosta said that if a patient isn’t responding to one class of medication, he pivots to a treatment better aligned with their phenotype. “That could mean switching from a GLP-1 to a medication like [naltrexone/bupropion] or trying a new method altogether,” he said. “The key is that the treatment decision is rooted in the patient’s biology, not just a reaction to short-term results. We also emphasize the importance of long-term follow-up and support.”

The goal isn’t just weight loss but also improved health and quality of life, Acosta said. “Whether through medication, surgery, or behavior change, what matters most is tailoring the care plan to each individual’s unique biology and needs.”

The new study received support from the Mayo Clinic Clinical Research Trials Unit, Vivus Inc., and Phenomix Sciences. Acosta is supported by a National Institutes of Health grant.

Acosta is a co-founder and inventor of intellectual property licensed to Phenomix Sciences Inc.; has served as a consultant for Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Boehringer Ingelheim, Currax Pharmaceuticals, Nestlé, Bausch Health, and Rare Diseases; and has received research support or had contracts with Vivus Inc., Satiogen Pharmaceuticals, Boehringer Ingelheim, and Rhythm Pharmaceuticals. Machineni has been involved in semaglutide and tirzepatide clinical trials and has been a consultant to Novo Nordisk, Eli Lilly and Company, and Rhythm Pharmaceuticals. Kushner is on the scientific advisory board for Novo Nordisk.

A version of this article appeared on Medscape.com.

Low rates of retained gastric contents were seen in endoscopy patients on GLP-1 receptor agonists ( RAs), a retrospective multicenter cross-sectional analysis reported in The American Journal of Gastroenterology. Moreover, most instances occurred in patients using the drugs for type 2 diabetes (T2D) rather than for weight loss alone.

The findings suggest adopting an individualized approach rather than universal preoperative withholding of GLP-1 RAs before endoscopy, concluded Jennifer Phan, MD, medical director of the Hoag Advanced Endoscopy Center in Newport Beach, California, and colleagues. These agents are associated with slowed gastric emptying, possibly raising the risk for pulmonary aspiration. The study identified comorbid uncontrolled T2D as a risk factor for retained gastric contents.

Recommendations from gastroenterological societies and the American Society of Anesthesiologists (ASA) differ regarding pre-endoscopic holding of these ubiquitous agents used for obesity and T2D. “Many patients undergo routine endoscopic procedures, and there was concern from the anesthesia safety perspective for retained gastric contents,” Phan told GI & Hepatology News. “At first these events were seen in a handful of cases; however, out of precaution this resulted in a statement from the ASA recommending that patients hold their GLP-1 medications for at least 1 week prior to a routine endoscopic procedure.”

That guidance resulted in protocol changes within endoscopy units, cancelled procedures, and potential delays in patient care. “We wanted to study whether this concern was clinically valid and to help identify which subgroup of patients are at highest risk in order to best inform anesthesia and endoscopy practices,” Phan added.

The ASA updated its guidance in 2023.

The current study aligns with other research showing that rates of clinically relevant retained gastric contents are < 10%, Phan said. For instance, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures. AGA guidance suggests an individual approach for each patient on a GLP-1 RA rather than a blanket statement on how to manage all patients taking the medications.

“Our initial hypothesis was that the rates of clinically relevant retained gastric contents in patients on GLP-1 RA medications would be low,” Phan noted. “This was born out of anecdotal experience of the limited number of aborted procedures we experienced before the ASA statement.” 

Her group also hypothesized that the indication for which the GLP-1 RA was prescribed would be important, with patients taking GLP-1 RA medications for diabetes potentially having a higher likelihood of retained contents given the concomitant propensity for delayed gastric motility related to uncontrolled hyperglycemia.

 

The Study

The investigators identified 815 patients on confirmed GLP-1 RA medications of various types receiving endoscopy from 2021 to 2023 at four centers. Demographics, prescribing practices, and procedure outcomes were captured. GLP-1 RA management of preoperative holding was retroactively classified per ASA guidance.

Of the 815 patients (mean age, 67.7 years; 57.7% women; 53.9% White individuals), 70 (8.7%) exhibited retained gastric contents on endoscopy. Of these 65 (93%) had T2D with a median A1c of 6.5%. Among those with retained contents, most had a minimal (10, 14.3%) or moderate (31, 44.3%) amount of food retained, although 29 (41.4%) had a large quantity. Only one patient required unplanned intubation because of a large quantity of residual content, and none had aspiration events.

In multivariate analysis, the odds ratio of retention in those with diabetes was 4.1. “Given the predominance of diabetes in those with retained gastric contents, we highlight the potential to risk-stratify patients who require further preprocedural consideration,” the authors wrote.

Those with GLP-1 RA held per ASA guidance (406, 49.8%) were less likely to have retained contents (4.4% vs 12.7%; P < .001), but no significant differences for intubation (0% vs 2%; P = .53) or aborting procedure rates (28% vs 18%; P = .40) due to gastric retention were observed.

On multivariable analysis, the likelihood of food retention increased by 36% (95% CI, 1.15-1.60) for every 1% increase in glycosylated hemoglobin after adjusting for GLP-1 RA type and preoperative medication hold.

“Our study can help to differentiate which patients can be at largest risk for retained gastric contents,” Phan said, noting the impact of increasing percentages of A1C. “There’s a 36% increased likelihood of food retention in patients on GLP-1 medications, so a blanket policy to hold GLP-1s in patients who are nondiabetic and taking the medication for obesity may not be the best approach. But if patients have uncontrolled hyperglycemia, then an approach of caution is clinically valid.” In that context, holding the GLP-1 RA injection or lengthening the preoperative clear-liquid diet policy should be considered.

She noted that the study results are generalizable because the study was conducted across multiple types of hospital systems, both university and county, and included all types of GLP-1 RA.

Offering an anesthesiologist’s perspective on the study, Paul Potnuru, MD, an assistant professor in the Department of Anesthesiology, Critical Care, and Pain Medicine at UTHealth Houston and not involved in the study, called the findings “somewhat reassuring” but said the risk for aspiration was still a consideration.

A recent review, however, reported that the risk for GLP-1 RA-associated pulmonary aspiration was low.

Potnuru acknowledged that the original ASA guidance on preoperative GLP-1 RA cessation led to some confusion. “There were not a lot of data on the issue, but some studies found that even with stopping GLP-1s 2 weeks preoperatively some patients still retained gastric content,” he told GI & Hepatology News.

A study at his center recently reported that 56% of GLP-1 RA users had increased pre-anesthesia residual gastric content compared with 19% of nonusers.

From the anesthesiologist’s clinical vantage point, the margin of safety is an issue even if aspiration risk is low. “If there’s a 1 in 1000 chance or even a 1 in 3000 chance, that can be considered too high,” Potnuru said.

He further noted that the current study included only 815 patients, not nearly enough for definitive data. In addition, a retrospective study based on medical records can’t really capture all the real-world procedural changes made in the operating room. “It’s common for anesthesiologists not to document all cases of intubation, for example,” he said.

While the ideal is a completely empty stomach, he agreed that a practical alternative to stopping GLP-1 RA therapy, especially that prescribed for diabetes, would be a 24-hour liquid diet, which would clear the stomach quickly. “If you stop these drugs in patients taking them for diabetes, you get a worsening of their glycemic control,” he said.

He noted that patients have different risk tolerances, with some willing to go ahead even if ultrasound shows gastric retention, while some opt to cancel.

Prospective studies are needed, Potnuru added, “because you find more if you know what you’re looking for.” His center is starting a clinical trial in 150 patients to assess the impact of a 24-hour, liquids-only diet on gastric retention.

According to Phan, other research is following GLP-1 RA users undergoing colonoscopy. “Future studies can look at the added value of point-of-care abdominal ultrasound to see if it increases precision preoperative management in these patients on GLP-1 medications.”

Other groups are examining the safety of these agents in the general context of sedation. “It’s worth noting that the studies are being done on currently available medications and may not apply to future medications such as triple agonists or anti-amylins that may come on the market in the near future,” Phan said.

This study received no financial support. Neither the study authors nor Potnuru had any conflicts of interest.

A version of this article appeared on Medscape.com.

Low rates of retained gastric contents were seen in endoscopy patients on GLP-1 receptor agonists ( RAs), a retrospective multicenter cross-sectional analysis reported in The American Journal of Gastroenterology. Moreover, most instances occurred in patients using the drugs for type 2 diabetes (T2D) rather than for weight loss alone.

The findings suggest adopting an individualized approach rather than universal preoperative withholding of GLP-1 RAs before endoscopy, concluded Jennifer Phan, MD, medical director of the Hoag Advanced Endoscopy Center in Newport Beach, California, and colleagues. These agents are associated with slowed gastric emptying, possibly raising the risk for pulmonary aspiration. The study identified comorbid uncontrolled T2D as a risk factor for retained gastric contents.

Recommendations from gastroenterological societies and the American Society of Anesthesiologists (ASA) differ regarding pre-endoscopic holding of these ubiquitous agents used for obesity and T2D. “Many patients undergo routine endoscopic procedures, and there was concern from the anesthesia safety perspective for retained gastric contents,” Phan told GI & Hepatology News. “At first these events were seen in a handful of cases; however, out of precaution this resulted in a statement from the ASA recommending that patients hold their GLP-1 medications for at least 1 week prior to a routine endoscopic procedure.”

That guidance resulted in protocol changes within endoscopy units, cancelled procedures, and potential delays in patient care. “We wanted to study whether this concern was clinically valid and to help identify which subgroup of patients are at highest risk in order to best inform anesthesia and endoscopy practices,” Phan added.

The ASA updated its guidance in 2023.

The current study aligns with other research showing that rates of clinically relevant retained gastric contents are < 10%, Phan said. For instance, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures. AGA guidance suggests an individual approach for each patient on a GLP-1 RA rather than a blanket statement on how to manage all patients taking the medications.

“Our initial hypothesis was that the rates of clinically relevant retained gastric contents in patients on GLP-1 RA medications would be low,” Phan noted. “This was born out of anecdotal experience of the limited number of aborted procedures we experienced before the ASA statement.” 

Her group also hypothesized that the indication for which the GLP-1 RA was prescribed would be important, with patients taking GLP-1 RA medications for diabetes potentially having a higher likelihood of retained contents given the concomitant propensity for delayed gastric motility related to uncontrolled hyperglycemia.

 

The Study

The investigators identified 815 patients on confirmed GLP-1 RA medications of various types receiving endoscopy from 2021 to 2023 at four centers. Demographics, prescribing practices, and procedure outcomes were captured. GLP-1 RA management of preoperative holding was retroactively classified per ASA guidance.

Of the 815 patients (mean age, 67.7 years; 57.7% women; 53.9% White individuals), 70 (8.7%) exhibited retained gastric contents on endoscopy. Of these 65 (93%) had T2D with a median A1c of 6.5%. Among those with retained contents, most had a minimal (10, 14.3%) or moderate (31, 44.3%) amount of food retained, although 29 (41.4%) had a large quantity. Only one patient required unplanned intubation because of a large quantity of residual content, and none had aspiration events.

In multivariate analysis, the odds ratio of retention in those with diabetes was 4.1. “Given the predominance of diabetes in those with retained gastric contents, we highlight the potential to risk-stratify patients who require further preprocedural consideration,” the authors wrote.

Those with GLP-1 RA held per ASA guidance (406, 49.8%) were less likely to have retained contents (4.4% vs 12.7%; P < .001), but no significant differences for intubation (0% vs 2%; P = .53) or aborting procedure rates (28% vs 18%; P = .40) due to gastric retention were observed.

On multivariable analysis, the likelihood of food retention increased by 36% (95% CI, 1.15-1.60) for every 1% increase in glycosylated hemoglobin after adjusting for GLP-1 RA type and preoperative medication hold.

“Our study can help to differentiate which patients can be at largest risk for retained gastric contents,” Phan said, noting the impact of increasing percentages of A1C. “There’s a 36% increased likelihood of food retention in patients on GLP-1 medications, so a blanket policy to hold GLP-1s in patients who are nondiabetic and taking the medication for obesity may not be the best approach. But if patients have uncontrolled hyperglycemia, then an approach of caution is clinically valid.” In that context, holding the GLP-1 RA injection or lengthening the preoperative clear-liquid diet policy should be considered.

She noted that the study results are generalizable because the study was conducted across multiple types of hospital systems, both university and county, and included all types of GLP-1 RA.

Offering an anesthesiologist’s perspective on the study, Paul Potnuru, MD, an assistant professor in the Department of Anesthesiology, Critical Care, and Pain Medicine at UTHealth Houston and not involved in the study, called the findings “somewhat reassuring” but said the risk for aspiration was still a consideration.

A recent review, however, reported that the risk for GLP-1 RA-associated pulmonary aspiration was low.

Potnuru acknowledged that the original ASA guidance on preoperative GLP-1 RA cessation led to some confusion. “There were not a lot of data on the issue, but some studies found that even with stopping GLP-1s 2 weeks preoperatively some patients still retained gastric content,” he told GI & Hepatology News.

A study at his center recently reported that 56% of GLP-1 RA users had increased pre-anesthesia residual gastric content compared with 19% of nonusers.

From the anesthesiologist’s clinical vantage point, the margin of safety is an issue even if aspiration risk is low. “If there’s a 1 in 1000 chance or even a 1 in 3000 chance, that can be considered too high,” Potnuru said.

He further noted that the current study included only 815 patients, not nearly enough for definitive data. In addition, a retrospective study based on medical records can’t really capture all the real-world procedural changes made in the operating room. “It’s common for anesthesiologists not to document all cases of intubation, for example,” he said.

While the ideal is a completely empty stomach, he agreed that a practical alternative to stopping GLP-1 RA therapy, especially that prescribed for diabetes, would be a 24-hour liquid diet, which would clear the stomach quickly. “If you stop these drugs in patients taking them for diabetes, you get a worsening of their glycemic control,” he said.

He noted that patients have different risk tolerances, with some willing to go ahead even if ultrasound shows gastric retention, while some opt to cancel.

Prospective studies are needed, Potnuru added, “because you find more if you know what you’re looking for.” His center is starting a clinical trial in 150 patients to assess the impact of a 24-hour, liquids-only diet on gastric retention.

According to Phan, other research is following GLP-1 RA users undergoing colonoscopy. “Future studies can look at the added value of point-of-care abdominal ultrasound to see if it increases precision preoperative management in these patients on GLP-1 medications.”

Other groups are examining the safety of these agents in the general context of sedation. “It’s worth noting that the studies are being done on currently available medications and may not apply to future medications such as triple agonists or anti-amylins that may come on the market in the near future,” Phan said.

This study received no financial support. Neither the study authors nor Potnuru had any conflicts of interest.

A version of this article appeared on Medscape.com.

Low rates of retained gastric contents were seen in endoscopy patients on GLP-1 receptor agonists ( RAs), a retrospective multicenter cross-sectional analysis reported in The American Journal of Gastroenterology. Moreover, most instances occurred in patients using the drugs for type 2 diabetes (T2D) rather than for weight loss alone.

The findings suggest adopting an individualized approach rather than universal preoperative withholding of GLP-1 RAs before endoscopy, concluded Jennifer Phan, MD, medical director of the Hoag Advanced Endoscopy Center in Newport Beach, California, and colleagues. These agents are associated with slowed gastric emptying, possibly raising the risk for pulmonary aspiration. The study identified comorbid uncontrolled T2D as a risk factor for retained gastric contents.

Recommendations from gastroenterological societies and the American Society of Anesthesiologists (ASA) differ regarding pre-endoscopic holding of these ubiquitous agents used for obesity and T2D. “Many patients undergo routine endoscopic procedures, and there was concern from the anesthesia safety perspective for retained gastric contents,” Phan told GI & Hepatology News. “At first these events were seen in a handful of cases; however, out of precaution this resulted in a statement from the ASA recommending that patients hold their GLP-1 medications for at least 1 week prior to a routine endoscopic procedure.”

That guidance resulted in protocol changes within endoscopy units, cancelled procedures, and potential delays in patient care. “We wanted to study whether this concern was clinically valid and to help identify which subgroup of patients are at highest risk in order to best inform anesthesia and endoscopy practices,” Phan added.

The ASA updated its guidance in 2023.

The current study aligns with other research showing that rates of clinically relevant retained gastric contents are < 10%, Phan said. For instance, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures. AGA guidance suggests an individual approach for each patient on a GLP-1 RA rather than a blanket statement on how to manage all patients taking the medications.

“Our initial hypothesis was that the rates of clinically relevant retained gastric contents in patients on GLP-1 RA medications would be low,” Phan noted. “This was born out of anecdotal experience of the limited number of aborted procedures we experienced before the ASA statement.” 

Her group also hypothesized that the indication for which the GLP-1 RA was prescribed would be important, with patients taking GLP-1 RA medications for diabetes potentially having a higher likelihood of retained contents given the concomitant propensity for delayed gastric motility related to uncontrolled hyperglycemia.

 

The Study

The investigators identified 815 patients on confirmed GLP-1 RA medications of various types receiving endoscopy from 2021 to 2023 at four centers. Demographics, prescribing practices, and procedure outcomes were captured. GLP-1 RA management of preoperative holding was retroactively classified per ASA guidance.

Of the 815 patients (mean age, 67.7 years; 57.7% women; 53.9% White individuals), 70 (8.7%) exhibited retained gastric contents on endoscopy. Of these 65 (93%) had T2D with a median A1c of 6.5%. Among those with retained contents, most had a minimal (10, 14.3%) or moderate (31, 44.3%) amount of food retained, although 29 (41.4%) had a large quantity. Only one patient required unplanned intubation because of a large quantity of residual content, and none had aspiration events.

In multivariate analysis, the odds ratio of retention in those with diabetes was 4.1. “Given the predominance of diabetes in those with retained gastric contents, we highlight the potential to risk-stratify patients who require further preprocedural consideration,” the authors wrote.

Those with GLP-1 RA held per ASA guidance (406, 49.8%) were less likely to have retained contents (4.4% vs 12.7%; P < .001), but no significant differences for intubation (0% vs 2%; P = .53) or aborting procedure rates (28% vs 18%; P = .40) due to gastric retention were observed.

On multivariable analysis, the likelihood of food retention increased by 36% (95% CI, 1.15-1.60) for every 1% increase in glycosylated hemoglobin after adjusting for GLP-1 RA type and preoperative medication hold.

“Our study can help to differentiate which patients can be at largest risk for retained gastric contents,” Phan said, noting the impact of increasing percentages of A1C. “There’s a 36% increased likelihood of food retention in patients on GLP-1 medications, so a blanket policy to hold GLP-1s in patients who are nondiabetic and taking the medication for obesity may not be the best approach. But if patients have uncontrolled hyperglycemia, then an approach of caution is clinically valid.” In that context, holding the GLP-1 RA injection or lengthening the preoperative clear-liquid diet policy should be considered.

She noted that the study results are generalizable because the study was conducted across multiple types of hospital systems, both university and county, and included all types of GLP-1 RA.

Offering an anesthesiologist’s perspective on the study, Paul Potnuru, MD, an assistant professor in the Department of Anesthesiology, Critical Care, and Pain Medicine at UTHealth Houston and not involved in the study, called the findings “somewhat reassuring” but said the risk for aspiration was still a consideration.

A recent review, however, reported that the risk for GLP-1 RA-associated pulmonary aspiration was low.

Potnuru acknowledged that the original ASA guidance on preoperative GLP-1 RA cessation led to some confusion. “There were not a lot of data on the issue, but some studies found that even with stopping GLP-1s 2 weeks preoperatively some patients still retained gastric content,” he told GI & Hepatology News.

A study at his center recently reported that 56% of GLP-1 RA users had increased pre-anesthesia residual gastric content compared with 19% of nonusers.

From the anesthesiologist’s clinical vantage point, the margin of safety is an issue even if aspiration risk is low. “If there’s a 1 in 1000 chance or even a 1 in 3000 chance, that can be considered too high,” Potnuru said.

He further noted that the current study included only 815 patients, not nearly enough for definitive data. In addition, a retrospective study based on medical records can’t really capture all the real-world procedural changes made in the operating room. “It’s common for anesthesiologists not to document all cases of intubation, for example,” he said.

While the ideal is a completely empty stomach, he agreed that a practical alternative to stopping GLP-1 RA therapy, especially that prescribed for diabetes, would be a 24-hour liquid diet, which would clear the stomach quickly. “If you stop these drugs in patients taking them for diabetes, you get a worsening of their glycemic control,” he said.

He noted that patients have different risk tolerances, with some willing to go ahead even if ultrasound shows gastric retention, while some opt to cancel.

Prospective studies are needed, Potnuru added, “because you find more if you know what you’re looking for.” His center is starting a clinical trial in 150 patients to assess the impact of a 24-hour, liquids-only diet on gastric retention.

According to Phan, other research is following GLP-1 RA users undergoing colonoscopy. “Future studies can look at the added value of point-of-care abdominal ultrasound to see if it increases precision preoperative management in these patients on GLP-1 medications.”

Other groups are examining the safety of these agents in the general context of sedation. “It’s worth noting that the studies are being done on currently available medications and may not apply to future medications such as triple agonists or anti-amylins that may come on the market in the near future,” Phan said.

This study received no financial support. Neither the study authors nor Potnuru had any conflicts of interest.

A version of this article appeared on Medscape.com.

Obstructive sleep apnea (OSA) was associated with a significantly increased risk for adverse health outcomes and health care resource use among military personnel in the US, according to data from about 120,000 active-duty service members.

OSA and other clinical sleep disorders are common among military personnel, driven in part by demanding, nontraditional work schedules that can exacerbate sleep problems, but OSA’s impact in this population has not been well-studied, Emerson M. Wickwire, PhD, of the University of Maryland School of Medicine, Baltimore, and colleagues wrote in a new paper published in Chest.

In the current health economic climate of increasing costs and limited resources, the economic aspects of sleep disorders have never been more important, Wickwire said in an interview. The data in this study are the first to quantify the health and utilization burden of OSA in the US military and can support military decision-makers regarding allocation of scarce resources, he said.

To assess the burden of OSA in the military, they reviewed fully de-identified data from 59,203 active-duty military personnel with diagnoses of OSA and compared them with 59,203 active-duty military personnel without OSA. The participants ranged in age from 18 to 64 years; 7.4% were women and 64.5% were white individuals. Study outcomes included new diagnoses of physical and psychological health conditions, as well as health care resource use in the first year after the index date.

About one third of the participants were in the Army (38.7%), 25.6% were in the Air Force, 23.5% were in the Navy, 5.8% were in the Marines, 5.7% were in the Coast Guard, and 0.7% were in the Public Health Service.

Over the 1-year study period, military personnel with OSA diagnoses were significantly more likely to experience new physical and psychological adverse events than control individuals without OSA, based on proportional hazards models. The physical conditions with the greatest increased risk in the OSA group were traumatic brain injury and cardiovascular disease (which included acute myocardial infarction, atrial fibrillation, ischemic heart disease, and peripheral procedures), with hazard ratios (HRs) 3.27 and 2.32, respectively. The psychological conditions with the greatest increased risk in the OSA group vs control individuals were posttraumatic stress disorder (PTSD) and anxiety (HR, 4.41, and HR, 3.35, respectively).

Individuals with OSA also showed increased use of healthcare resources compared with control individuals without OSA, with an additional 170,511 outpatient visits, 66 inpatient visits, and 1,852 emergency department visits.

 

Don’t Discount OSA in Military Personnel

“From a clinical perspective, these findings underscore the importance of recognizing OSA as a critical risk factor for a wide array of physical and psychological health outcomes,” the researchers wrote in their discussion.

The results highlight the need for more clinical attention to patient screening, triage, and delivery of care, but efforts are limited by the documented shortage of sleep specialists in the military health system, they noted.

Key limitations of the study include the use of an administrative claims data source, which did not include clinical information such as disease severity or daytime symptoms, and the nonrandomized, observational study design, Wickwire told this news organization.

Looking ahead, the researchers at the University of Maryland School of Medicine and the Uniformed Services University, Bethesda, Maryland, are launching a new trial to assess the clinical effectiveness and cost-effectiveness of telehealth visits for military beneficiaries diagnosed with OSA as a way to manage the shortage of sleep specialists in the military health system, according to a press release from the University of Maryland.

“Although the association between poor sleep and traumatic stress is well-known, present results highlight striking associations between sleep apnea and posttraumatic stress disorder, traumatic brain injury, and musculoskeletal injuries, which are key outcomes from the military perspective,” Wickwire told this news organization.

“Our most important clinical recommendation is for healthcare providers to be on alert for signs and symptoms of OSA, including snoring, daytime sleepiness, and morning dry mouth,” said Wickwire. “Primary care and mental health providers should be especially attuned,” he added.

 

Results Not Surprising, but Research Gaps Remain

“The sleep health of active-duty military personnel is not only vital for optimal military performance but also impacts the health of Veterans after separation from the military,” said Q. Afifa Shamim-Uzzaman, MD, an associate professor and a sleep medicine specialist at the University of Michigan, Ann Arbor, Michigan, in an interview.

The current study identifies increased utilization of healthcare resources by active-duty personnel with sleep apnea, and outcomes were not surprising, said Shamim-Uzzaman, who is employed by the Veterans’ Health Administration, but was not involved in the current study.

The association between untreated OSA and medical and psychological comorbidities such as cardiovascular disease, diabetes, and mood disorders such as depression and anxiety is well-known, Shamim-Uzzaman said. “Patients with depression who also have sleep disturbances are at higher risk for suicide — the strength of this association is such that it led the Veterans’ Health Administration to mandate suicide screening for Veterans seen in its sleep clinics,” he added.

“We also know that untreated OSA is associated with excessive daytime sleepiness, slowed reaction times, and increased risk of motor vehicle accidents, all of which can contribute to sustaining injuries such as traumatic brain injury,” said Shamim-Uzzaman. “Emerging evidence also suggests that sleep disruption prior to exposure to trauma increases the risk of developing PTSD. Therefore, it is not surprising that patients with sleep apnea would have higher healthcare utilization for non-OSA conditions than those without sleep apnea,” he noted.

In clinical practice, the study underscores the importance of identifying and managing sleep health in military personnel, who frequently work nontraditional schedules with long, sustained shifts in grueling conditions not conducive to healthy sleep, Shamim-Uzzaman told this news organization. “Although the harsh work environments that our active-duty military endure come part and parcel with the job, clinicians caring for these individuals should ask specifically about their sleep and working schedules to optimize sleep as best as possible; this should include, but not be limited to, screening and testing for sleep disordered breathing and insomnia,” he said.

The current study has several limitations, including the inability to control for smoking or alcohol use, which are common in military personnel and associated with increased morbidity, said Shamim-Uzzaman. The study also did not assess the impact of other confounding factors, such as sleep duration and daytime sleepiness, that could impact the results, especially the association of OSA and traumatic brain injury, he noted. “More research is needed to assess the impact of these factors as well as the effect of treatment of OSA on comorbidities and healthcare utilization,” he said.

This study was supported by the Military Health Services Research Program.

Wickwire’s institution had received research funding from the American Academy of Sleep Medicine Foundation, Department of Defense, Merck, National Institutes of Health/National Institute on Aging, ResMed, the ResMed Foundation, and the SRS Foundation. Wickwire disclosed serving as a scientific consultant to Axsome Therapeutics, Dayzz, Eisai, EnsoData, Idorsia, Merck, Nox Health, Primasun, Purdue, and ResMed and is an equity shareholder in Well Tap.

Shamim-Uzzaman is an employee of the Veterans’ Health Administration.

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

Obstructive sleep apnea (OSA) was associated with a significantly increased risk for adverse health outcomes and health care resource use among military personnel in the US, according to data from about 120,000 active-duty service members.

OSA and other clinical sleep disorders are common among military personnel, driven in part by demanding, nontraditional work schedules that can exacerbate sleep problems, but OSA’s impact in this population has not been well-studied, Emerson M. Wickwire, PhD, of the University of Maryland School of Medicine, Baltimore, and colleagues wrote in a new paper published in Chest.

In the current health economic climate of increasing costs and limited resources, the economic aspects of sleep disorders have never been more important, Wickwire said in an interview. The data in this study are the first to quantify the health and utilization burden of OSA in the US military and can support military decision-makers regarding allocation of scarce resources, he said.

To assess the burden of OSA in the military, they reviewed fully de-identified data from 59,203 active-duty military personnel with diagnoses of OSA and compared them with 59,203 active-duty military personnel without OSA. The participants ranged in age from 18 to 64 years; 7.4% were women and 64.5% were white individuals. Study outcomes included new diagnoses of physical and psychological health conditions, as well as health care resource use in the first year after the index date.

About one third of the participants were in the Army (38.7%), 25.6% were in the Air Force, 23.5% were in the Navy, 5.8% were in the Marines, 5.7% were in the Coast Guard, and 0.7% were in the Public Health Service.

Over the 1-year study period, military personnel with OSA diagnoses were significantly more likely to experience new physical and psychological adverse events than control individuals without OSA, based on proportional hazards models. The physical conditions with the greatest increased risk in the OSA group were traumatic brain injury and cardiovascular disease (which included acute myocardial infarction, atrial fibrillation, ischemic heart disease, and peripheral procedures), with hazard ratios (HRs) 3.27 and 2.32, respectively. The psychological conditions with the greatest increased risk in the OSA group vs control individuals were posttraumatic stress disorder (PTSD) and anxiety (HR, 4.41, and HR, 3.35, respectively).

Individuals with OSA also showed increased use of healthcare resources compared with control individuals without OSA, with an additional 170,511 outpatient visits, 66 inpatient visits, and 1,852 emergency department visits.

 

Don’t Discount OSA in Military Personnel

“From a clinical perspective, these findings underscore the importance of recognizing OSA as a critical risk factor for a wide array of physical and psychological health outcomes,” the researchers wrote in their discussion.

The results highlight the need for more clinical attention to patient screening, triage, and delivery of care, but efforts are limited by the documented shortage of sleep specialists in the military health system, they noted.

Key limitations of the study include the use of an administrative claims data source, which did not include clinical information such as disease severity or daytime symptoms, and the nonrandomized, observational study design, Wickwire told this news organization.

Looking ahead, the researchers at the University of Maryland School of Medicine and the Uniformed Services University, Bethesda, Maryland, are launching a new trial to assess the clinical effectiveness and cost-effectiveness of telehealth visits for military beneficiaries diagnosed with OSA as a way to manage the shortage of sleep specialists in the military health system, according to a press release from the University of Maryland.

“Although the association between poor sleep and traumatic stress is well-known, present results highlight striking associations between sleep apnea and posttraumatic stress disorder, traumatic brain injury, and musculoskeletal injuries, which are key outcomes from the military perspective,” Wickwire told this news organization.

“Our most important clinical recommendation is for healthcare providers to be on alert for signs and symptoms of OSA, including snoring, daytime sleepiness, and morning dry mouth,” said Wickwire. “Primary care and mental health providers should be especially attuned,” he added.

 

Results Not Surprising, but Research Gaps Remain

“The sleep health of active-duty military personnel is not only vital for optimal military performance but also impacts the health of Veterans after separation from the military,” said Q. Afifa Shamim-Uzzaman, MD, an associate professor and a sleep medicine specialist at the University of Michigan, Ann Arbor, Michigan, in an interview.

The current study identifies increased utilization of healthcare resources by active-duty personnel with sleep apnea, and outcomes were not surprising, said Shamim-Uzzaman, who is employed by the Veterans’ Health Administration, but was not involved in the current study.

The association between untreated OSA and medical and psychological comorbidities such as cardiovascular disease, diabetes, and mood disorders such as depression and anxiety is well-known, Shamim-Uzzaman said. “Patients with depression who also have sleep disturbances are at higher risk for suicide — the strength of this association is such that it led the Veterans’ Health Administration to mandate suicide screening for Veterans seen in its sleep clinics,” he added.

“We also know that untreated OSA is associated with excessive daytime sleepiness, slowed reaction times, and increased risk of motor vehicle accidents, all of which can contribute to sustaining injuries such as traumatic brain injury,” said Shamim-Uzzaman. “Emerging evidence also suggests that sleep disruption prior to exposure to trauma increases the risk of developing PTSD. Therefore, it is not surprising that patients with sleep apnea would have higher healthcare utilization for non-OSA conditions than those without sleep apnea,” he noted.

In clinical practice, the study underscores the importance of identifying and managing sleep health in military personnel, who frequently work nontraditional schedules with long, sustained shifts in grueling conditions not conducive to healthy sleep, Shamim-Uzzaman told this news organization. “Although the harsh work environments that our active-duty military endure come part and parcel with the job, clinicians caring for these individuals should ask specifically about their sleep and working schedules to optimize sleep as best as possible; this should include, but not be limited to, screening and testing for sleep disordered breathing and insomnia,” he said.

The current study has several limitations, including the inability to control for smoking or alcohol use, which are common in military personnel and associated with increased morbidity, said Shamim-Uzzaman. The study also did not assess the impact of other confounding factors, such as sleep duration and daytime sleepiness, that could impact the results, especially the association of OSA and traumatic brain injury, he noted. “More research is needed to assess the impact of these factors as well as the effect of treatment of OSA on comorbidities and healthcare utilization,” he said.

This study was supported by the Military Health Services Research Program.

Wickwire’s institution had received research funding from the American Academy of Sleep Medicine Foundation, Department of Defense, Merck, National Institutes of Health/National Institute on Aging, ResMed, the ResMed Foundation, and the SRS Foundation. Wickwire disclosed serving as a scientific consultant to Axsome Therapeutics, Dayzz, Eisai, EnsoData, Idorsia, Merck, Nox Health, Primasun, Purdue, and ResMed and is an equity shareholder in Well Tap.

Shamim-Uzzaman is an employee of the Veterans’ Health Administration.

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

Obstructive sleep apnea (OSA) was associated with a significantly increased risk for adverse health outcomes and health care resource use among military personnel in the US, according to data from about 120,000 active-duty service members.

OSA and other clinical sleep disorders are common among military personnel, driven in part by demanding, nontraditional work schedules that can exacerbate sleep problems, but OSA’s impact in this population has not been well-studied, Emerson M. Wickwire, PhD, of the University of Maryland School of Medicine, Baltimore, and colleagues wrote in a new paper published in Chest.

In the current health economic climate of increasing costs and limited resources, the economic aspects of sleep disorders have never been more important, Wickwire said in an interview. The data in this study are the first to quantify the health and utilization burden of OSA in the US military and can support military decision-makers regarding allocation of scarce resources, he said.

To assess the burden of OSA in the military, they reviewed fully de-identified data from 59,203 active-duty military personnel with diagnoses of OSA and compared them with 59,203 active-duty military personnel without OSA. The participants ranged in age from 18 to 64 years; 7.4% were women and 64.5% were white individuals. Study outcomes included new diagnoses of physical and psychological health conditions, as well as health care resource use in the first year after the index date.

About one third of the participants were in the Army (38.7%), 25.6% were in the Air Force, 23.5% were in the Navy, 5.8% were in the Marines, 5.7% were in the Coast Guard, and 0.7% were in the Public Health Service.

Over the 1-year study period, military personnel with OSA diagnoses were significantly more likely to experience new physical and psychological adverse events than control individuals without OSA, based on proportional hazards models. The physical conditions with the greatest increased risk in the OSA group were traumatic brain injury and cardiovascular disease (which included acute myocardial infarction, atrial fibrillation, ischemic heart disease, and peripheral procedures), with hazard ratios (HRs) 3.27 and 2.32, respectively. The psychological conditions with the greatest increased risk in the OSA group vs control individuals were posttraumatic stress disorder (PTSD) and anxiety (HR, 4.41, and HR, 3.35, respectively).

Individuals with OSA also showed increased use of healthcare resources compared with control individuals without OSA, with an additional 170,511 outpatient visits, 66 inpatient visits, and 1,852 emergency department visits.

 

Don’t Discount OSA in Military Personnel

“From a clinical perspective, these findings underscore the importance of recognizing OSA as a critical risk factor for a wide array of physical and psychological health outcomes,” the researchers wrote in their discussion.

The results highlight the need for more clinical attention to patient screening, triage, and delivery of care, but efforts are limited by the documented shortage of sleep specialists in the military health system, they noted.

Key limitations of the study include the use of an administrative claims data source, which did not include clinical information such as disease severity or daytime symptoms, and the nonrandomized, observational study design, Wickwire told this news organization.

Looking ahead, the researchers at the University of Maryland School of Medicine and the Uniformed Services University, Bethesda, Maryland, are launching a new trial to assess the clinical effectiveness and cost-effectiveness of telehealth visits for military beneficiaries diagnosed with OSA as a way to manage the shortage of sleep specialists in the military health system, according to a press release from the University of Maryland.

“Although the association between poor sleep and traumatic stress is well-known, present results highlight striking associations between sleep apnea and posttraumatic stress disorder, traumatic brain injury, and musculoskeletal injuries, which are key outcomes from the military perspective,” Wickwire told this news organization.

“Our most important clinical recommendation is for healthcare providers to be on alert for signs and symptoms of OSA, including snoring, daytime sleepiness, and morning dry mouth,” said Wickwire. “Primary care and mental health providers should be especially attuned,” he added.

 

Results Not Surprising, but Research Gaps Remain

“The sleep health of active-duty military personnel is not only vital for optimal military performance but also impacts the health of Veterans after separation from the military,” said Q. Afifa Shamim-Uzzaman, MD, an associate professor and a sleep medicine specialist at the University of Michigan, Ann Arbor, Michigan, in an interview.

The current study identifies increased utilization of healthcare resources by active-duty personnel with sleep apnea, and outcomes were not surprising, said Shamim-Uzzaman, who is employed by the Veterans’ Health Administration, but was not involved in the current study.

The association between untreated OSA and medical and psychological comorbidities such as cardiovascular disease, diabetes, and mood disorders such as depression and anxiety is well-known, Shamim-Uzzaman said. “Patients with depression who also have sleep disturbances are at higher risk for suicide — the strength of this association is such that it led the Veterans’ Health Administration to mandate suicide screening for Veterans seen in its sleep clinics,” he added.

“We also know that untreated OSA is associated with excessive daytime sleepiness, slowed reaction times, and increased risk of motor vehicle accidents, all of which can contribute to sustaining injuries such as traumatic brain injury,” said Shamim-Uzzaman. “Emerging evidence also suggests that sleep disruption prior to exposure to trauma increases the risk of developing PTSD. Therefore, it is not surprising that patients with sleep apnea would have higher healthcare utilization for non-OSA conditions than those without sleep apnea,” he noted.

In clinical practice, the study underscores the importance of identifying and managing sleep health in military personnel, who frequently work nontraditional schedules with long, sustained shifts in grueling conditions not conducive to healthy sleep, Shamim-Uzzaman told this news organization. “Although the harsh work environments that our active-duty military endure come part and parcel with the job, clinicians caring for these individuals should ask specifically about their sleep and working schedules to optimize sleep as best as possible; this should include, but not be limited to, screening and testing for sleep disordered breathing and insomnia,” he said.

The current study has several limitations, including the inability to control for smoking or alcohol use, which are common in military personnel and associated with increased morbidity, said Shamim-Uzzaman. The study also did not assess the impact of other confounding factors, such as sleep duration and daytime sleepiness, that could impact the results, especially the association of OSA and traumatic brain injury, he noted. “More research is needed to assess the impact of these factors as well as the effect of treatment of OSA on comorbidities and healthcare utilization,” he said.

This study was supported by the Military Health Services Research Program.

Wickwire’s institution had received research funding from the American Academy of Sleep Medicine Foundation, Department of Defense, Merck, National Institutes of Health/National Institute on Aging, ResMed, the ResMed Foundation, and the SRS Foundation. Wickwire disclosed serving as a scientific consultant to Axsome Therapeutics, Dayzz, Eisai, EnsoData, Idorsia, Merck, Nox Health, Primasun, Purdue, and ResMed and is an equity shareholder in Well Tap.

Shamim-Uzzaman is an employee of the Veterans’ Health Administration.

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