Risks of GLP-1RA Therapy Related to Endoscopy: Three Studies and GLP1RA Nutrition Pearls

A recent Nutrition Pearls with one of our nutritionists, Baily Koch, as a moderator was very good: Christy Figueredo – Navigating GLP-1 Use in Pediatrics (episode 33, 58 minutes)


A Faccisorusso et al. Clin Gastroenterol Hepatol 2025; 23: 715-725. Open access! Effects of Glucagon-Like Peptide-1 Receptor Agonists on Upper Gastrointestinal Endoscopy: A Meta-Analysis

This is one of three articles discussing the issue of GLP-1RAs and potential complications with upper endoscopy. Faccisourruso et al performed a meta-analysis that included 13 studies (of 177 studies) involving a total of 84,065 patients.

Key findings:

  • Patients receiving GLP-1RA therapy exhibited significantly higher rates of retained gastric contents (RGC) (OR, 5.56)
  • Rates of aborted and repeated procedures were higher in the GLP-1RA user group. The absolute risk of aborted procedure was 1% in GLP-1RA users compared to 0.3% in non-users. The absolute risk of a repeated procedure was 2% vs 1% respectively.
  • No significant differences were found in AE and aspiration rates between the 2 groups (OR, 4.04 and OR, 1.75 respectively). The absolute risk of aspiration was 0.3% in GLP1-RA users compared to 0.2% in non-GLP1-RA group
  • Adverse events were higher in GLP-1RA users (0.3%) compared to non-users (0.1%)

In their discussion, the authors note that an “individualized approach based on the indication of GLP-1RA use (withholding the drug in patients with diabetes could lead to more harm)…a potential stragegy could be to place patients on a liquid diet the day before endoscopy, thus prolonging the duration of fasting for solid for at least 12 hours.”

The related articles:

My take: The totality of these studies confirms the increased risk of retained gastric contents in patients receiving GLP-1RAs. This in turn increases the need to abort/reschedule cases and may result in very a low increased risk of aspiration. To mitigate this risk, it may be sufficient to implement a liquid diet the day before endoscopy (avoiding solid foods for at least 12 hours prior to endoscopy). This is in agreement with the recent AGA Rapid Clinical Practice Update (see post below).

Related article on utility of GLP-1RAs: David Kessler, NY Times  5/7/25: In a World of Addictive Foods, We Need GLP-1s

Like millions of others, I was caught between what the food industry has done to make the American diet unhealthy and addictive and what my metabolism could accommodate.

We may now be at the brink of reclaiming our health. New and highly effective anti-obesity medications known as GLP-1s have revolutionized our understanding of weight loss and of obesity itself. These drugs alone are not a panacea for the obesity crisis that has engulfed the nation, and we should not mistake them for one. But their effectiveness underscores the fact that being overweight or obese was never the result of a lack of willpower

GLP-1s are revolutionary drugs that can drastically reduce caloric intake and improve health in a way I didn’t expect I would ever see. Now we need to complete that revolution by taking on the food industry and its engineered foods that are contributing to some of the most harmful health issues America faces today.”

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

VISION 5-Year Study Results: Safety of Vonoprazan in Erosive Esophagitis

N Uemura et al. Clin Gastroenterol Hepatol 2025; 23: 748-757. Open Access! Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study

Background: Potassium-competitive acid blockers, such as vonoprazan, provide more potent gastric acid suppression than proton pump inhibitors. However, long-term safety data are lacking for vonoprazan in patients with healed erosive esophagitis. This study with 208 patients provides long-term data on the use of a vonoprazan.

Methods: Open-label study. Patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). 

Key findings–Adverse effects:

  • No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group
  • At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%)
  • proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar
  • Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL)

Key finding –Efficacy:

  • Overall, the cumulative EE recurrence over 260 weeks was lower in the vonoprazan group (10.8% ) vs the lansoprazole group (38.0%) (P = .001)  

Discussion Points:

  • “Annual endoscopies and biopsies performed in the VISION study are considered objective approaches for detecting upper gastrointestinal diseases and variable lesions, as well as gastric mucosa morphological changes in areas without endoscopically apparent lesions…Although the proportions of patients with parietal cell protrusion and foveolar hyperplasia were higher in the vonoprazan group than in the lansoprazole group over 5 years, the clinical significance of these findings is unclear.”
  • “The safety profiles of vonoprazan and lansoprazole were also comparable, suggesting that long-term use of vonoprazan is as safe as PPIs.”

My take: This study provides some reassurance regarding the risk of using vonoprazan & other potassium-competitive acid blockers. The benefits of controlling erosive esophagitis may outweigh potential safety risks of long-term use. Nevertheless, it will be a while before this class of medications is used extensively in the pediatric age group.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Head-to-Head: Tirzepatide Outperforms Semaglutide

LA Aronne et al. NEJM 2025; DOI: 10.1056/NEJMoa2416394. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity

Methods: In this phase 3b, open-label, controlled “SURMOUNT-5” trial, adult participants (n=751) with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks

Key findings:

Discussion Points:

“With both treatments in our trial, as weight reduction increased, greater improvements occurred in cardiometabolic risk factors, including blood pressure, glycemia, and lipid levels, which is consistent with the findings in previous reports.17 The mean differences between tirzepatide and semaglutide in the cardiometabolic risk factors may be clinically relevant considering that reductions in systolic blood pressure of 2 to 5 mm Hg have been shown to reduce the risk of cardiovascular events.”

” As typically observed with incretin-based therapies, gastrointestinal adverse events were predominantly mild to moderate in severity, occurred mostly during dose escalation, and led to treatment discontinuation more often with semaglutide than with tirzepatide.”

My take (borrowed from the authors):  “Treatment with tirzepatide, a dual GIP and GLP-1 receptor agonist, was superior to treatment with semaglutide, a selective GLP-1 receptor agonist, with respect to reduction in body weight and waist circumference.”

Related blog posts:

Upadacitinib’s Effectiveness for Perianal Fistulizing Crohn’s Disease

J-F Colombel et al. Clinical Gastroenterology and Hepatology, Volume 23, Issue 6, 1019 – 1029. Open Access! Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials

Methods: This post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in the following studies: phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials. It was noted that there were 1021 patients in U-EXCEL and U-EXCEED; 143 (14.0%) had any fistulas at baseline (66 draining). Most (n = 128) had perianal fistulas (56 draining).

Key findings:

  • Fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo
These slides from Figure 1 show the resolution of drainage in perianal draining fistulas, closure of external perianal fistula openings, and closure of external openings for any fistula at week 12 of the induction trials and week 52 of the maintenance trial.

Discussion points:

  • Patients with draining fistulas often experience higher disease burden
  • Most patients in U-EXCEL and U-EXCEED had failed at least 2 prior biologic treatments (which often included anti-TNF therapy), reflecting a more refractory and difficult-to-treat population in CD
  • Despite the presence of perianal disease, patients with fistulizing CD treated with upadacitinib showed concurrent improvements in CD symptoms (CDAI, SF, and APS), luminal disease (endoscopic response and SES-CD), and markers of inflammation

My take: This study shows that upadacitinib is more effective than placebo; however, the majority of patients continued with ongoing perianal disease.

Related blog posts:

Increase in Irritable Bowel Syndrome During COVID Pandemic

CV Almario et al. Neurogastroenterology and Motility; https://doi.org/10.1111/nmo.70020. Trends in Prevalence of Rome IV Disorders of Gut-Brain Interaction During the COVID-19 Pandemic: Results From a Nationally Representative Sample of Over 160,000 People in the US

Methods: From May 2020 to May 2022, the authors performed a series of cross-sectional online surveys among a representative sample of adults ≥ 18 years old in the US (n=160,154). We administered Rome IV gastroduodenal and bowel DGBI questionnaires.

Key findings:

  •  During the COVID-19 pandemic, the prevalence of irritable bowel syndrome (IBS) increased from 6.1% [May 2020] to 11.0% [May 2022]
  • In addition, the prevalence of chronic idiopathic constipation (CIC) increased mildly from 6.0% [May 2020] to 6.4% [May 2022]
  • No changes in prevalence were seen for the other examined gastroduodenal and bowel disorders of gut-brain interaction (DGBI)

My take: This study identified increases in the prevalence of IBS during COVID. Increases in IBS following other enteric infections (eg. norovirus, shigella, campylobacter) has been shown previously as well.

Related blog posts:

Rice Fields in Northern Thailand

David Rubin: Linking Inflammatory Bowel Disease and Mental Health Through the Gut Microbiome

At this year’s DDW, Dr. David Rubin discussed the connection between inflammatory bowel disease and mental health via the microbiome. He shared his slides: Linking Inflammatory Bowel Disease and Mental Health Through the Gut Microbiome

Here are 15 of his 37 slides:

The Guardian: UnitedHealth Secretly Paid Nursing Homes to Reduce Hospital Transfers

The Guardian 5/21/25:
Revealed: UnitedHealth secretly paid nursing homes to reduce hospital transfers

An excerpt:

UnitedHealth Group, the nation’s largest healthcare conglomerate, has secretly paid nursing homes thousands in bonuses to help slash hospital transfers for ailing residents – part of a series of cost-cutting tactics that has saved the company millions, but at times risked residents’ health, a Guardian investigation has found…

Those secret bonuses have been paid out as part of a UnitedHealth program that stations the company’s own medical teams in nursing homes and pushes them to cut care expenses for residents covered by the insurance giant.

In several cases identified by the Guardian, nursing home residents who needed immediate hospital care under the program failed to receive it, after interventions from UnitedHealth staffer…UnitedHealth said the suggestion that its employees have prevented hospital transfers “is verifiably false”. It said its bonus payments to nursing homes help prevent unnecessary hospitalizations that are costly and dangerous to patients and that its partnerships with nursing homes improve health outcomes…

To reduce residents’ hospital visits, UnitedHealth has offered nursing homes an array of financial sweeteners…

Two current and three former UnitedHealth nurse practitioners told the Guardian that UnitedHealth managers pressed nurse practitioners to persuade Medicare Advantage members to change their “code status” to DNR even when patients had clearly expressed a desire that all available treatments be used to keep them alive...

UnitedHealth’s insurance arm covers millions more Medicare Advantage seniors than any of its rivals

Commentary from Dr. Glaucomflecken account on X: https://x.com/i/status/1925348490680340979

My take: Healthcare insurance companies are incentivized to act as financial institutions and gatekeepers/third party administrators. This often compromises and delays patient care.

Related blog posts:

Essential Summer Safety Tips for Preventing Drowning

Yesterday, a ICU colleague indicated that she really does not like to work on summer holiday weekends. While she is a hard worker, what she doesn’t like is seeing kids with drowning and firework injuries. All of a sudden a happy time becomes tragic. With that in mind, here are a few tips to prevent drowning.

From Strong4Life: “Practicing water safety for kids of all ages is crucial because drowning is a leading cause of death in children from birth through the teen years. And drowning is often quick and silent.”

Also, firearm deaths are the leading cause of death in children in the U.S. and motor vehicle accidents are second. So, firearms need to be secured and drive safely on the way to the pool, lake, river or beach.

Related blog posts:

How Putting America First is Undermining Health Outcomes Here and Globally

CP Duggan, ZA Bhutta. NEJM 2025; DOI: 10.1056/NEJMp2503243. “Putting America First” — Undermining Health for Populations at Home and Abroad

This article initially lays out the historical context of U.S. involvement in global health dating back to aiding famine in Belgium (1917), WHO (1948), USAID (1961). Also, the CDC and NIH have played important roles following WWII. Subsequently, the commentary outlines the impact of dismantling U.S global health efforts. In the two related articles cited afterwards, it is clear that the cuts to foreign aid and other DOGE activities may result in millions of deaths and at the same time expand the federal deficit.

An excerpt:

In the initial months of the Trump administration, numerous executive orders have led to a chaotic dismantling of U.S. foreign-assistance and global health efforts. These orders have already had, and will continue to have, severe adverse effects on vulnerable populations globally. But they also have serious implications for people in the United States…

Often missing from these success stories are the financial and health-related benefits these programs have had in the United States….One of the earliest and most fundamental examples of reciprocal innovation was the discovery and implementation of oral rehydration therapy (ORT)…Widespread use of ORT has helped drive substantial reductions in childhood deaths from diarrhea and has led to a new standard of care for childhood diarrhea in high-income countries and to commercial products in the United States…

Perhaps no program epitomizes these dual advantages better than the President’s Emergency Plan for AIDS Relief (PEPFAR). Early in the HIV epidemic, the NIH promoted multinational scientific collaborations to identify the virus, develop effective treatments, and implement global prevention and treatment programs, which led to PEPFAR’s creation in 2003. PEPFAR has saved 26 million lives, and economic growth in countries with PEPFAR programs has benefited the United States and other trading partners…[and] have contributed enormously to current knowledge about HIV and AIDS.

Another essential initiative, the FIC — the NIH institute responsible for supporting research training and partnerships in global health — has …directly benefited health in the United States by advancing early cancer detection and the development of sickle cell disease therapies, point-of-care diagnostics for infectious diseases, and treatments for child malnutrition. More than three quarters of FIC grants involve a U.S. grantee or investigator, which further emphasizes the institute’s direct benefits to the U.S. economy…

Since U.S. foreign assistance accounts for about 1% of the federal budget, we are skeptical of cost-savings–based arguments for its elimination…

The Trump administration’s gutting of USAID and other foreign-assistance programs marks a break from decades of evidence-based practices that have improved lives throughout the world. In addition to pushing millions of people into poverty and leading to an estimated 160,000 or more avoidable child deaths each year,4 these reforms will undermine health and the economy in the United States…

Withdrawal from the WHO reduces the United States’ ability to influence reform and restructuring of the world’s global health coordinating body. The elimination of U.S. funding for Gavi, the Vaccine Alliance, also endangers the health of vulnerable populations internationally and in the United States…

Critical to the success of advocacy efforts will be evidence of the ways in which the withdrawal of foreign aid and global disengagement undermine health and economic well-being in the United States and threaten global health and economic security.

My take: By the time the extent of the damage is understood, it will be too late to fix what this administration has destroyed. The toll in terms of death and suffering both in the U.S. and abroad will be hard to justify and not further the aim of making ‘America First.’

Related articles:

  1. D Wallace-Wells, NY Times 5/8/25: The $200 Billion Gamble: Bill Gates’s Plan to Wind Down His Foundation “He is committing the foundation to 20 more years of generous aid, more than $200 billion in total, targeting health and human development…The news comes at a time that will seem to many as a perilous one, given the Trump administration’s recent assault on foreign aid and indeed on the idea of global generosity itself….The journal Nature suggested that an overall cessation of U.S. aid funding could result in roughly 25 million additional deaths over 15 years.”
  2. J Riedl, The Atlantic 5/8/25: The Actual Math Behind DOGE’s Cuts “As an effort to meaningfully reduce federal spending, however, DOGE remains wholly unserious…The DOGE website now claims $165 billion in savings. However, it still details only a fraction of the supposed cuts, and earlier accounting errors have given way to new ones…Even assuming that the website’s stated savings have become twice as accurate as they were in February, annual savings would reach perhaps $15 billion, or 0.2 percent of federal spending…Total federal outlays in February and March were $86 billion (or 7 percent) higher than the levels from the same months a year ago, when adjusted for timing shifts. This spending growth—approximately $500 billion at an annualized rate—continues to be driven by the three-quarters of federal spending allocated to Social Security, Medicare, Medicaid, defense, veterans’ benefits, and interest costs. These massive expenses have been untouched by DOGE’s focus on small but controversial targets such as DEI contracts and Politico subscriptions…The bad news is that the project seems quite likely to expand long-term budget deficits. Slashing IRS enforcement will embolden tax evasion and reduce revenues by hundreds of billions of dollars over the decade. Laying off Department of Education employees who ensure collection of student-loan repayments will increase the deficit. Illegally terminated federal employees are already being reinstated with full back pay, leaving the government with little to show for its trouble besides mounting legal fees…None of this is to say that DOGE has failed. Musk might not have followed through on his unfocused and evolving promises to eliminate payment errors, balance the entire budget, and implement regulatory reform. But he has successfully given the White House cover to purge and intimidate the civil service, helped Congress justify exorbitant tax cuts, rewarded MAGA voters with revenge against their perceived enemies, and granted himself the ability to access sensitive government data and possibly ensure his companies’ continued government contracts. Sure, annual budget deficits remain on track to double over the next decade. But if you thought DOGE was really about cutting costs, you were never in on the joke.”
View of the Chattahoochee River from Don While Memorial Park, Sandy Springs, Ga

EAT-Lancet Diet Associated with Reduced Risk of MASLD

From the commentary: “In 2019, the EAT-Lancet Commission on Food, Plant, and Health proposed a planetary health diet, known as the EAT-Lancet reference diet, that promotes human health and sustainable food production globally…and recommends fruits, vegetables, whole grains, plant-based proteins (eg. legumes, nuts) and unsaturated plant oils, with limited or moderate amounts of animal-based proteins such as meat and dairy….[it] has been associated with multiple health benefits, including reducing the risks of type 2 diabetes, cardiovascular disease, certain cancers, and all-cause mortality.”

Methods: This prospective multicohort study comprised more than 191,000 adults from several cohorts. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included.

Key findings:

  • Participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles with HR ranging in different cohorts from 0.73 to 0.87
  • Liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (β = −5.895

My take (borrowed from the authors): Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Related blog posts: