Obesity

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Roughly 8.6% of the 17.4 million US veterans live in poverty. About 11.1% are considered food insecure (ie, unable to acquire adequate food for ≥1 household members), with another 5.3% considered very food insecure (ie, eating patterns of ≥1 household members were disrupted and their food intake was reduced at least some time during the year). Compared with nonveterans, veterans are 7.4% more likely to be food insecure.¹ This high prevalence of food insecurity and poverty has a negative impact on veteran diets.

Veterans’ diets contained more added sugars and solid fats and scored lower compared with nonveterans when assessed for diet quality with the Healthy Eating Index.² Veterans have a higher prevalence of diet-related chronic disease, including diabetes, hypertension, and obesity compared with the nonveterans.^3-5 Given the critical role of diet in health and disease risk, enhancing diet quality among veterans has garnered significant attention and calls to action.^2,6,7 While there are many factors that contribute to diet, any veteran can receive a consultation or self-refer to receive nutrition counseling effective for improving diet quality, within the US Department of Veterans Affairs (VA).

The NOVA food classification system describes diet quality by categorizing food items by processing methods and ingredients into 4 food groups.⁸ The first is unprocessed and minimally processed items (MPFs) such as fresh fruits, vegetables, and meats. MPFs consist of whole foods which can also be minimally processed (eg, chopping, drying, grinding, heating, chilling). Culinary processed foods (CPFs) are processed foods for cooking (eg, salt, butter, and vinegar) and are typically eaten in small quantities along with MPFs. Processed foods (PRFs) include canned and smoked foods, while ultra-processed foods (UPFs) are distinguished by industrial ingredients, requiring specialized tools and processing techniques, and hyper-palatability related to color, flavor, and packaging.⁸ Examples of UPFs include mass-produced breads found at grocery stores, prepackaged snacks and meals, and hydrogenated oils. UPF consumption is associated with higher risk for negative cardiometabolic outcomes, common mental disorders, and all-cause mortality.⁹ To date, only a study by Powell et al has used the NOVA classification system in a veteran population, and it was limited to a comparison of the price of UPFs and veteran body mass index (BMI).¹⁰ Therefore, it remains unknown what percentage of total energy intake (TEI) comes from UPFs in the diets of veterans.

This study sought to quantify the proportion of TEI from UPFs among a sample of patients from the VA Phoenix Health Care System (VAPHCS). Results from a 2021 global meta-analysis reveal that the US and United Kingdom have the highest intakes of UPFs in the world.¹¹ Specifically, within the US, 15 studies with 234,890 participants reveal that the majority of TEI (about 55%) comes from UPFs.¹¹ We hypothesized that this veteran sample would have a higher proportion of TEI from UPFs, possibly due to a higher prevalence of poverty and food insecurity among veterans compared with nonveterans.¹ If the percentage of TEI coming from UPF is higher or even similar to nonveterans, further efforts to increase veterans’ use of the available nutritional services would be warranted to minimize nutrition-related disease among veterans.

Methods

This is a cross-sectional, secondary data analysis of baseline 3-day food records collected from 2017 to 2020 from 92 patients recruited at VAPHCS to participate in a whole-food plant-based diet study.¹² The original study was reviewed and approved by the VAPHCS Institutional Review Board (1593830). Recruitment methods included clinician recommendation, a recorded advertisement played while phone calls were on hold, and flyers distributed throughout VAPHCS. Patients were included if they were aged 18 to 90 years, had a BMI 25.1 to 39.9, had a diagnosis of nutrition-related chronic disease (hypertension, diabetes, or hyperlipidemia), an interest and desire to make a lifestyle change, active telephone contact information (either landline or cell phone), no contraindication to be on a whole-food plant-based diet, access to transportation and a functioning kitchen, ability to prepare meals independently, access to a computer or tablet with internet access, and a digital camera or smartphone. Exclusion criteria included significant unplanned weight loss within 6 months, uncontrolled insulin-dependent diabetes with a current hemoglobin A_1c > 9%, pregnancy/lactation, taking prescribed weight loss medication, currently following a diet (eg, plant-based diet, vegan, or medical weight loss program diet), celiac disease diagnosed within 6 months, end-stage hepatic disease or renal disease requiring dialysis, active cancer or receiving chemotherapy or radiation therapy, active alcohol or substance use disorder, history of eating disorders, fasting triglyceride level > 350 mg/dL, any psychological issues that prevent adherence, inability to speak English, limited mobility, and homeless or in housing with limited kitchen access. A baseline 3-day food record was collected from the participants and used in this secondary analysis.

Diet Analysis

Food records were analyzed using Esha Research Food Processor 4.0 to identify calorie and macronutrient information. To limit bias, food items were coded independently by 2 researchers into 4 food processing groups determined by the NOVA classification: MPF, CPF, PRF, and UPF.⁸ When possible, specific ingredient information was collected using internet searches for brand product websites. Initial coding had an 89% agreement rate for food item coding between the 2 researchers. As coding was done in duplicate, a third researcher resolved disagreements. The number of food items for each processing group was determined and the mean (SD) percentage of TEI for each NOVA group was provided across participants. A 1-way analysis of variance and Tukey Multiple Comparisons Test were used to determine significance between groups with an α = .05 using Prism V9.

Results

Of the 92 participants in the original study, only 79 met inclusion criteria and had baseline diet data. The 79 veterans had a mean (SD) age of 61 (13) years and 59 (75%) were male (Table 1). Mean (SD) TEI was 1921 (815) kcal. The mean (SD) percentage of calories from carbohydrate, fat, and protein were 46% (21%), 39% (20%), and 16% (6%), respectively (Table 2).

A mean (SD) of 36 (12) food items were analyzed from the 3-day food records. The majority of food items were UPFs (56%), 33% were MPFs, 8% were PRFs, and 3% were CPFs. In total, 75% of TEI came from UPFs (P < .001); only 14% of TEI came from minimally processed foods (Figure).

Discussion

To our knowledge, this is the first analysis of UPF consumption among US veterans. TEIs coming from UPFs appear to be about 20% higher among veterans compared to nonveterans: 75% vs 55%.¹¹ Coupled with high UPF consumption, MPFs (14%) and PRFs (9%) represent smaller sources of TEI among surveyed veterans. Top caloric sources of UPFs in the US include sandwiches (including burgers), sweet bakery products, savory snacks, pizza, sweetened beverages, and breads, rolls, and tortillas, and likely reflect the major sources of UPFs in the veteran diet.¹³ As the statistical comparison between the veteran data and nonveteran data is not feasible in the present study, a future study with a much larger sample size would be needed for a direct comparison.

While the exact cause of higher UPF consumption among sampled veterans remains unknown and likely multifactorial (eg, cost, food insecurity, access, cooking skills, nutrition knowledge), veterans can receive a consult or self-refer to a registered dietitian nutritionist (RDN) for nutrition education. Counseling has been shown to be an effective way to improve diet quality and increase daily fruit and vegetable intake.¹⁴ High consumption of UPFs, which are generally energy-dense and nutrient-poor, contributes to the low diet quality observed in veterans, and future research examining the relationship between UPF intake and overall diet quality among veterans is warranted.^2,15 As nutrition knowledge is associated with higher diet quality among veterans, increased use of nutrition services (ie, nutrition education or food supplement programs) has the potential to influence consumption of MPFs and decrease consumption of UPFs.¹⁶ Subsequently, UPF-targeted interventions developed by VA RDNs hold the promise to decrease consumption of UPFs and increase intake of MPFs and PRFs.

Veterans have a high prevalence of diabetes, hypertension, and obesity.⁹ The high UPF intake observed in this sample of veterans may increase the risk for these chronic diseases and overall mortality. The high percentage of TEI from UPFs among veterans is also of concern not only due to potential negative health outcomes, but also associated costs of treating veterans with multimorbidities.¹⁷ Targeting UPF intake via nutritional education may promote health and decrease the financial burden needed to support the health of veterans.

Improving veteran health and well-being, including enhancing health care accessibility in underserved areas, are pivotal objectives of the VA strategic plan for 2026 to 2030. Public policy aims to tackle food insecurity within the veteran population during the first 5 years of civilian life.¹⁸ In alignment with the White House Strategy on Hunger, Nutrition, and Health, VA established a Food Security Office (FSO) in 2023. The FSO mission is to use an interdisciplinary approach to provide resources to ensure veteran food security and create an environment where all veterans are food and nutrition secure.

Limitations

This study has several limitations. As the Food Processor software database does not include all brand items, similar brands were used to mirror the nutrient profile. While food records are common among veteran diet studies, accuracy may be reduced due to self-reporting bias.¹⁹ Different interpretation of the NOVA classification designation for various food items is possible, however, 89% of foods were coded the same by the research team which suggests high accuracy in food coding. Specific ingredient information was not collected from the 3-day food records; thus, these records were not produced in such a way to improve the accuracy of the NOVA classification designation. This study was limited by its small sample size (N = 79); although, this analysis is larger than other studies of UPF consumption in the US.^20,21 In addition, the generalizability of this study is limited as this population sample was from a single VA hospital and may not reflect the overall veteran population. Participants in this study were recruited only from those receiving VA care, thus their diet quality may not represent the quality consumed by veterans not participating in VA services. Further research on UPF consumption among veterans is warranted with a larger, more representative study sample size.

Conclusions

As this is the highest observed UPF intake documented in the US, these results should be of concern for the VA and its RDNs. More research is needed to better understand why UPF consumption is so high among veterans, what barriers veterans face to decreasing UPF consumption, and what intervention(s) veterans would welcome to improve their diet quality. Presently, veterans are provided with access to a variety of effective nutrition education and counseling options and should be encouraged to use these services. VA RDNs should be aware of the high intake of UPFs in the veteran population and familiarize themselves with education and counseling strategies that promote behavior change to replace UPFs with more nutrient-dense foods choices.

Roughly 8.6% of the 17.4 million US veterans live in poverty. About 11.1% are considered food insecure (ie, unable to acquire adequate food for ≥1 household members), with another 5.3% considered very food insecure (ie, eating patterns of ≥1 household members were disrupted and their food intake was reduced at least some time during the year). Compared with nonveterans, veterans are 7.4% more likely to be food insecure.¹ This high prevalence of food insecurity and poverty has a negative impact on veteran diets.

Veterans’ diets contained more added sugars and solid fats and scored lower compared with nonveterans when assessed for diet quality with the Healthy Eating Index.² Veterans have a higher prevalence of diet-related chronic disease, including diabetes, hypertension, and obesity compared with the nonveterans.^3-5 Given the critical role of diet in health and disease risk, enhancing diet quality among veterans has garnered significant attention and calls to action.^2,6,7 While there are many factors that contribute to diet, any veteran can receive a consultation or self-refer to receive nutrition counseling effective for improving diet quality, within the US Department of Veterans Affairs (VA).

The NOVA food classification system describes diet quality by categorizing food items by processing methods and ingredients into 4 food groups.⁸ The first is unprocessed and minimally processed items (MPFs) such as fresh fruits, vegetables, and meats. MPFs consist of whole foods which can also be minimally processed (eg, chopping, drying, grinding, heating, chilling). Culinary processed foods (CPFs) are processed foods for cooking (eg, salt, butter, and vinegar) and are typically eaten in small quantities along with MPFs. Processed foods (PRFs) include canned and smoked foods, while ultra-processed foods (UPFs) are distinguished by industrial ingredients, requiring specialized tools and processing techniques, and hyper-palatability related to color, flavor, and packaging.⁸ Examples of UPFs include mass-produced breads found at grocery stores, prepackaged snacks and meals, and hydrogenated oils. UPF consumption is associated with higher risk for negative cardiometabolic outcomes, common mental disorders, and all-cause mortality.⁹ To date, only a study by Powell et al has used the NOVA classification system in a veteran population, and it was limited to a comparison of the price of UPFs and veteran body mass index (BMI).¹⁰ Therefore, it remains unknown what percentage of total energy intake (TEI) comes from UPFs in the diets of veterans.

This study sought to quantify the proportion of TEI from UPFs among a sample of patients from the VA Phoenix Health Care System (VAPHCS). Results from a 2021 global meta-analysis reveal that the US and United Kingdom have the highest intakes of UPFs in the world.¹¹ Specifically, within the US, 15 studies with 234,890 participants reveal that the majority of TEI (about 55%) comes from UPFs.¹¹ We hypothesized that this veteran sample would have a higher proportion of TEI from UPFs, possibly due to a higher prevalence of poverty and food insecurity among veterans compared with nonveterans.¹ If the percentage of TEI coming from UPF is higher or even similar to nonveterans, further efforts to increase veterans’ use of the available nutritional services would be warranted to minimize nutrition-related disease among veterans.

Methods

This is a cross-sectional, secondary data analysis of baseline 3-day food records collected from 2017 to 2020 from 92 patients recruited at VAPHCS to participate in a whole-food plant-based diet study.¹² The original study was reviewed and approved by the VAPHCS Institutional Review Board (1593830). Recruitment methods included clinician recommendation, a recorded advertisement played while phone calls were on hold, and flyers distributed throughout VAPHCS. Patients were included if they were aged 18 to 90 years, had a BMI 25.1 to 39.9, had a diagnosis of nutrition-related chronic disease (hypertension, diabetes, or hyperlipidemia), an interest and desire to make a lifestyle change, active telephone contact information (either landline or cell phone), no contraindication to be on a whole-food plant-based diet, access to transportation and a functioning kitchen, ability to prepare meals independently, access to a computer or tablet with internet access, and a digital camera or smartphone. Exclusion criteria included significant unplanned weight loss within 6 months, uncontrolled insulin-dependent diabetes with a current hemoglobin A_1c > 9%, pregnancy/lactation, taking prescribed weight loss medication, currently following a diet (eg, plant-based diet, vegan, or medical weight loss program diet), celiac disease diagnosed within 6 months, end-stage hepatic disease or renal disease requiring dialysis, active cancer or receiving chemotherapy or radiation therapy, active alcohol or substance use disorder, history of eating disorders, fasting triglyceride level > 350 mg/dL, any psychological issues that prevent adherence, inability to speak English, limited mobility, and homeless or in housing with limited kitchen access. A baseline 3-day food record was collected from the participants and used in this secondary analysis.

Diet Analysis

Food records were analyzed using Esha Research Food Processor 4.0 to identify calorie and macronutrient information. To limit bias, food items were coded independently by 2 researchers into 4 food processing groups determined by the NOVA classification: MPF, CPF, PRF, and UPF.⁸ When possible, specific ingredient information was collected using internet searches for brand product websites. Initial coding had an 89% agreement rate for food item coding between the 2 researchers. As coding was done in duplicate, a third researcher resolved disagreements. The number of food items for each processing group was determined and the mean (SD) percentage of TEI for each NOVA group was provided across participants. A 1-way analysis of variance and Tukey Multiple Comparisons Test were used to determine significance between groups with an α = .05 using Prism V9.

Results

Of the 92 participants in the original study, only 79 met inclusion criteria and had baseline diet data. The 79 veterans had a mean (SD) age of 61 (13) years and 59 (75%) were male (Table 1). Mean (SD) TEI was 1921 (815) kcal. The mean (SD) percentage of calories from carbohydrate, fat, and protein were 46% (21%), 39% (20%), and 16% (6%), respectively (Table 2).

A mean (SD) of 36 (12) food items were analyzed from the 3-day food records. The majority of food items were UPFs (56%), 33% were MPFs, 8% were PRFs, and 3% were CPFs. In total, 75% of TEI came from UPFs (P < .001); only 14% of TEI came from minimally processed foods (Figure).

Discussion

To our knowledge, this is the first analysis of UPF consumption among US veterans. TEIs coming from UPFs appear to be about 20% higher among veterans compared to nonveterans: 75% vs 55%.¹¹ Coupled with high UPF consumption, MPFs (14%) and PRFs (9%) represent smaller sources of TEI among surveyed veterans. Top caloric sources of UPFs in the US include sandwiches (including burgers), sweet bakery products, savory snacks, pizza, sweetened beverages, and breads, rolls, and tortillas, and likely reflect the major sources of UPFs in the veteran diet.¹³ As the statistical comparison between the veteran data and nonveteran data is not feasible in the present study, a future study with a much larger sample size would be needed for a direct comparison.

While the exact cause of higher UPF consumption among sampled veterans remains unknown and likely multifactorial (eg, cost, food insecurity, access, cooking skills, nutrition knowledge), veterans can receive a consult or self-refer to a registered dietitian nutritionist (RDN) for nutrition education. Counseling has been shown to be an effective way to improve diet quality and increase daily fruit and vegetable intake.¹⁴ High consumption of UPFs, which are generally energy-dense and nutrient-poor, contributes to the low diet quality observed in veterans, and future research examining the relationship between UPF intake and overall diet quality among veterans is warranted.^2,15 As nutrition knowledge is associated with higher diet quality among veterans, increased use of nutrition services (ie, nutrition education or food supplement programs) has the potential to influence consumption of MPFs and decrease consumption of UPFs.¹⁶ Subsequently, UPF-targeted interventions developed by VA RDNs hold the promise to decrease consumption of UPFs and increase intake of MPFs and PRFs.

Veterans have a high prevalence of diabetes, hypertension, and obesity.⁹ The high UPF intake observed in this sample of veterans may increase the risk for these chronic diseases and overall mortality. The high percentage of TEI from UPFs among veterans is also of concern not only due to potential negative health outcomes, but also associated costs of treating veterans with multimorbidities.¹⁷ Targeting UPF intake via nutritional education may promote health and decrease the financial burden needed to support the health of veterans.

Improving veteran health and well-being, including enhancing health care accessibility in underserved areas, are pivotal objectives of the VA strategic plan for 2026 to 2030. Public policy aims to tackle food insecurity within the veteran population during the first 5 years of civilian life.¹⁸ In alignment with the White House Strategy on Hunger, Nutrition, and Health, VA established a Food Security Office (FSO) in 2023. The FSO mission is to use an interdisciplinary approach to provide resources to ensure veteran food security and create an environment where all veterans are food and nutrition secure.

Limitations

This study has several limitations. As the Food Processor software database does not include all brand items, similar brands were used to mirror the nutrient profile. While food records are common among veteran diet studies, accuracy may be reduced due to self-reporting bias.¹⁹ Different interpretation of the NOVA classification designation for various food items is possible, however, 89% of foods were coded the same by the research team which suggests high accuracy in food coding. Specific ingredient information was not collected from the 3-day food records; thus, these records were not produced in such a way to improve the accuracy of the NOVA classification designation. This study was limited by its small sample size (N = 79); although, this analysis is larger than other studies of UPF consumption in the US.^20,21 In addition, the generalizability of this study is limited as this population sample was from a single VA hospital and may not reflect the overall veteran population. Participants in this study were recruited only from those receiving VA care, thus their diet quality may not represent the quality consumed by veterans not participating in VA services. Further research on UPF consumption among veterans is warranted with a larger, more representative study sample size.

Conclusions

As this is the highest observed UPF intake documented in the US, these results should be of concern for the VA and its RDNs. More research is needed to better understand why UPF consumption is so high among veterans, what barriers veterans face to decreasing UPF consumption, and what intervention(s) veterans would welcome to improve their diet quality. Presently, veterans are provided with access to a variety of effective nutrition education and counseling options and should be encouraged to use these services. VA RDNs should be aware of the high intake of UPFs in the veteran population and familiarize themselves with education and counseling strategies that promote behavior change to replace UPFs with more nutrient-dense foods choices.

Roughly 8.6% of the 17.4 million US veterans live in poverty. About 11.1% are considered food insecure (ie, unable to acquire adequate food for ≥1 household members), with another 5.3% considered very food insecure (ie, eating patterns of ≥1 household members were disrupted and their food intake was reduced at least some time during the year). Compared with nonveterans, veterans are 7.4% more likely to be food insecure.¹ This high prevalence of food insecurity and poverty has a negative impact on veteran diets.

Veterans’ diets contained more added sugars and solid fats and scored lower compared with nonveterans when assessed for diet quality with the Healthy Eating Index.² Veterans have a higher prevalence of diet-related chronic disease, including diabetes, hypertension, and obesity compared with the nonveterans.^3-5 Given the critical role of diet in health and disease risk, enhancing diet quality among veterans has garnered significant attention and calls to action.^2,6,7 While there are many factors that contribute to diet, any veteran can receive a consultation or self-refer to receive nutrition counseling effective for improving diet quality, within the US Department of Veterans Affairs (VA).

The NOVA food classification system describes diet quality by categorizing food items by processing methods and ingredients into 4 food groups.⁸ The first is unprocessed and minimally processed items (MPFs) such as fresh fruits, vegetables, and meats. MPFs consist of whole foods which can also be minimally processed (eg, chopping, drying, grinding, heating, chilling). Culinary processed foods (CPFs) are processed foods for cooking (eg, salt, butter, and vinegar) and are typically eaten in small quantities along with MPFs. Processed foods (PRFs) include canned and smoked foods, while ultra-processed foods (UPFs) are distinguished by industrial ingredients, requiring specialized tools and processing techniques, and hyper-palatability related to color, flavor, and packaging.⁸ Examples of UPFs include mass-produced breads found at grocery stores, prepackaged snacks and meals, and hydrogenated oils. UPF consumption is associated with higher risk for negative cardiometabolic outcomes, common mental disorders, and all-cause mortality.⁹ To date, only a study by Powell et al has used the NOVA classification system in a veteran population, and it was limited to a comparison of the price of UPFs and veteran body mass index (BMI).¹⁰ Therefore, it remains unknown what percentage of total energy intake (TEI) comes from UPFs in the diets of veterans.

This study sought to quantify the proportion of TEI from UPFs among a sample of patients from the VA Phoenix Health Care System (VAPHCS). Results from a 2021 global meta-analysis reveal that the US and United Kingdom have the highest intakes of UPFs in the world.¹¹ Specifically, within the US, 15 studies with 234,890 participants reveal that the majority of TEI (about 55%) comes from UPFs.¹¹ We hypothesized that this veteran sample would have a higher proportion of TEI from UPFs, possibly due to a higher prevalence of poverty and food insecurity among veterans compared with nonveterans.¹ If the percentage of TEI coming from UPF is higher or even similar to nonveterans, further efforts to increase veterans’ use of the available nutritional services would be warranted to minimize nutrition-related disease among veterans.

Methods

This is a cross-sectional, secondary data analysis of baseline 3-day food records collected from 2017 to 2020 from 92 patients recruited at VAPHCS to participate in a whole-food plant-based diet study.¹² The original study was reviewed and approved by the VAPHCS Institutional Review Board (1593830). Recruitment methods included clinician recommendation, a recorded advertisement played while phone calls were on hold, and flyers distributed throughout VAPHCS. Patients were included if they were aged 18 to 90 years, had a BMI 25.1 to 39.9, had a diagnosis of nutrition-related chronic disease (hypertension, diabetes, or hyperlipidemia), an interest and desire to make a lifestyle change, active telephone contact information (either landline or cell phone), no contraindication to be on a whole-food plant-based diet, access to transportation and a functioning kitchen, ability to prepare meals independently, access to a computer or tablet with internet access, and a digital camera or smartphone. Exclusion criteria included significant unplanned weight loss within 6 months, uncontrolled insulin-dependent diabetes with a current hemoglobin A_1c > 9%, pregnancy/lactation, taking prescribed weight loss medication, currently following a diet (eg, plant-based diet, vegan, or medical weight loss program diet), celiac disease diagnosed within 6 months, end-stage hepatic disease or renal disease requiring dialysis, active cancer or receiving chemotherapy or radiation therapy, active alcohol or substance use disorder, history of eating disorders, fasting triglyceride level > 350 mg/dL, any psychological issues that prevent adherence, inability to speak English, limited mobility, and homeless or in housing with limited kitchen access. A baseline 3-day food record was collected from the participants and used in this secondary analysis.

Diet Analysis

Food records were analyzed using Esha Research Food Processor 4.0 to identify calorie and macronutrient information. To limit bias, food items were coded independently by 2 researchers into 4 food processing groups determined by the NOVA classification: MPF, CPF, PRF, and UPF.⁸ When possible, specific ingredient information was collected using internet searches for brand product websites. Initial coding had an 89% agreement rate for food item coding between the 2 researchers. As coding was done in duplicate, a third researcher resolved disagreements. The number of food items for each processing group was determined and the mean (SD) percentage of TEI for each NOVA group was provided across participants. A 1-way analysis of variance and Tukey Multiple Comparisons Test were used to determine significance between groups with an α = .05 using Prism V9.

Results

Of the 92 participants in the original study, only 79 met inclusion criteria and had baseline diet data. The 79 veterans had a mean (SD) age of 61 (13) years and 59 (75%) were male (Table 1). Mean (SD) TEI was 1921 (815) kcal. The mean (SD) percentage of calories from carbohydrate, fat, and protein were 46% (21%), 39% (20%), and 16% (6%), respectively (Table 2).

A mean (SD) of 36 (12) food items were analyzed from the 3-day food records. The majority of food items were UPFs (56%), 33% were MPFs, 8% were PRFs, and 3% were CPFs. In total, 75% of TEI came from UPFs (P < .001); only 14% of TEI came from minimally processed foods (Figure).

Discussion

To our knowledge, this is the first analysis of UPF consumption among US veterans. TEIs coming from UPFs appear to be about 20% higher among veterans compared to nonveterans: 75% vs 55%.¹¹ Coupled with high UPF consumption, MPFs (14%) and PRFs (9%) represent smaller sources of TEI among surveyed veterans. Top caloric sources of UPFs in the US include sandwiches (including burgers), sweet bakery products, savory snacks, pizza, sweetened beverages, and breads, rolls, and tortillas, and likely reflect the major sources of UPFs in the veteran diet.¹³ As the statistical comparison between the veteran data and nonveteran data is not feasible in the present study, a future study with a much larger sample size would be needed for a direct comparison.

While the exact cause of higher UPF consumption among sampled veterans remains unknown and likely multifactorial (eg, cost, food insecurity, access, cooking skills, nutrition knowledge), veterans can receive a consult or self-refer to a registered dietitian nutritionist (RDN) for nutrition education. Counseling has been shown to be an effective way to improve diet quality and increase daily fruit and vegetable intake.¹⁴ High consumption of UPFs, which are generally energy-dense and nutrient-poor, contributes to the low diet quality observed in veterans, and future research examining the relationship between UPF intake and overall diet quality among veterans is warranted.^2,15 As nutrition knowledge is associated with higher diet quality among veterans, increased use of nutrition services (ie, nutrition education or food supplement programs) has the potential to influence consumption of MPFs and decrease consumption of UPFs.¹⁶ Subsequently, UPF-targeted interventions developed by VA RDNs hold the promise to decrease consumption of UPFs and increase intake of MPFs and PRFs.

Veterans have a high prevalence of diabetes, hypertension, and obesity.⁹ The high UPF intake observed in this sample of veterans may increase the risk for these chronic diseases and overall mortality. The high percentage of TEI from UPFs among veterans is also of concern not only due to potential negative health outcomes, but also associated costs of treating veterans with multimorbidities.¹⁷ Targeting UPF intake via nutritional education may promote health and decrease the financial burden needed to support the health of veterans.

Improving veteran health and well-being, including enhancing health care accessibility in underserved areas, are pivotal objectives of the VA strategic plan for 2026 to 2030. Public policy aims to tackle food insecurity within the veteran population during the first 5 years of civilian life.¹⁸ In alignment with the White House Strategy on Hunger, Nutrition, and Health, VA established a Food Security Office (FSO) in 2023. The FSO mission is to use an interdisciplinary approach to provide resources to ensure veteran food security and create an environment where all veterans are food and nutrition secure.

Limitations

This study has several limitations. As the Food Processor software database does not include all brand items, similar brands were used to mirror the nutrient profile. While food records are common among veteran diet studies, accuracy may be reduced due to self-reporting bias.¹⁹ Different interpretation of the NOVA classification designation for various food items is possible, however, 89% of foods were coded the same by the research team which suggests high accuracy in food coding. Specific ingredient information was not collected from the 3-day food records; thus, these records were not produced in such a way to improve the accuracy of the NOVA classification designation. This study was limited by its small sample size (N = 79); although, this analysis is larger than other studies of UPF consumption in the US.^20,21 In addition, the generalizability of this study is limited as this population sample was from a single VA hospital and may not reflect the overall veteran population. Participants in this study were recruited only from those receiving VA care, thus their diet quality may not represent the quality consumed by veterans not participating in VA services. Further research on UPF consumption among veterans is warranted with a larger, more representative study sample size.

Conclusions

As this is the highest observed UPF intake documented in the US, these results should be of concern for the VA and its RDNs. More research is needed to better understand why UPF consumption is so high among veterans, what barriers veterans face to decreasing UPF consumption, and what intervention(s) veterans would welcome to improve their diet quality. Presently, veterans are provided with access to a variety of effective nutrition education and counseling options and should be encouraged to use these services. VA RDNs should be aware of the high intake of UPFs in the veteran population and familiarize themselves with education and counseling strategies that promote behavior change to replace UPFs with more nutrient-dense foods choices.

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

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

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

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

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

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

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

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

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

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

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

Decrease Side Effects for Weight-Loss Success

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

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

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

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

The study was funded by Neurogastrx.

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

Decrease Side Effects for Weight-Loss Success

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

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

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

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

The study was funded by Neurogastrx.

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

Decrease Side Effects for Weight-Loss Success

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

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

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

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

The study was funded by Neurogastrx.

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

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.