Impact of Obesity Medications on Gastric Function

Abstract

Anti-Obesity Medications (AOM) include multiple classes of medications that can be used for the treatment of obesity which can be categorized as first generation, second generation and third generation AOM. First and Second generation AOM’s were used in a limited number of patients in clinical practice, but the introduction of the third generation of AOMs—semaglutide and tirzepatide, glucagon-like peptide-1 receptor agonist (GLP1-RA) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA), respectively, has led to significantly higher obesity treatment with AOMs. These medications are significantly more effective than first and second generation AOMs, however, they also have significant effects on gastrointestinal motility. This has led to a broader discussion on the use of these medications in patients undergoing anesthesia for surgical or endoscopic procedures. In this review we discuss the full-spectrum of anti-obesity medications, their impact on gastric motility, data on clinical outcomes in patients undergoing endoscopic procedures on GLP-1 RA and the current landscape of medical society guidelines for patients on GLP-1 RA undergoing endoscopic procedures.

Keywords

anti-obesity medications glucagon-like peptide-1 receptor agonist glucose-dependent insulinotropic polypeptide receptor agonist gastroparesis

Key Learning Points

Third-generation AOMs like semaglutide and tirzepatide achieve 15% to 21% weight loss but delay gastric emptying.

GLP-1 RAs increase residual gastric contents during endoscopy, yet aspiration risk remains low.

Guidelines suggest multiple options for managing patients on GLP-1 RA undergoing endoscopic procedures including liquid diets or ultrasound, which may be more effective than routine medication holds due to long half-lives.

Older AOMs have milder effects on gastric motility but less efficacy.

Introduction

The rate of obesity has risen substantially in the United States and is currently at 42.4%.¹ Obesity contributes to the development of many cardiometabolic and non-cardiometabolic diseases across multiple organ systems. Notably, obesity is one of the leading risk factors for developing type 2 diabetes when compared with genetic factors and lifestyle.² In addition each 5 kg/m² increase in BMI is correlated with a hazard ratio of 1.27 for coronary heart disease and 1.18 for stroke,³ and obesity may account for up to 14% of all cancer deaths in men and 20% of all cancer deaths in women.⁴ Moreover, in a meta-analysis including 21 studies and 381,655 patients, obesity was an independent risk factor for Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), with a risk ratio of 3.53 (95% CI, 2.48 to 5.03, P < .001) and each 1 unit BMI increment was associated with a 1.2 fold increased risk of MASLD.⁵

The first line therapy of obesity is lifestyle therapy, however even high intensity lifestyle therapy has limited weight loss with weight regain over time. One of the largest lifestyle intervention studies, the Look AHEAD trial demonstrated only 4.7% total body weight loss (TBWL) at 4 years despite 42 lifestyle therapy visits in the first year of therapy and continued follow-up care thereafter.⁶ First generation and second generation AOMs increased weight loss over lifestyle therapy alone with only moderate success and weight loss of 2.9% to 8.6% above lifestyle therapy alone.⁷ While semaglutide and tirzepatide were first approved to treat type 2 diabetes, their approvals for the indication of obesity significantly changed the anti-obesity medication landscape with much higher weight loss than the previous generations of AOMs. This landscape has further changed with the approval of semaglutide to treat cardiovascular disease and metabolic dysfunction associated steatohepatitis (MASH) and the approval of tirzepatide to treat obstructive sleep apnea (OSA), but also introduced new challenges due to gastrointestinal side effects. This article reviews anti-obesity medications and their effect on gastric motility.

Anti-Obesity Medications

First Generation AOMs

Phentermine

Phentermine (Adipex-P, Gate, Sellersville, PA) was the first AOM in 1959 to be approved by the FDA. Although its approval duration is for short term use of 3 months, it is commonly prescribed for long-term use.⁸ As a sympathomimetic, it stimulates the release of norepinephrine resulting in appetite suppression through central effects.⁷ In recent trials, participants saw a mean weight loss of 7.5 kg, with 46.2% and 22% achieving 5% and 10% TBWL respectively after 28 weeks.⁹ Recent studies evaluating the safety and effectiveness of long-term phentermine use, demonstrated greater initial and sustained weight loss without increased risk of stroke or death with continuous use for 6 months resulting in a mean TBWL of 9.6%.¹⁰ Significant adverse events (AE) include xerostomia, insomnia, headache, elevated blood pressure, mood impairment, palpitations, erectile dysfunction, as well as seizure.⁷

Orlistat

Orlistat (Xenical, Cheplapharm, Greifswald, Germany), initially introduced in 1999, acts by reversibly inhibiting gastric and pancreatic lipases which prevents the hydrolysis of triglycerides, resulting in reduced triglyceride and fatty acid absorption. This blocks 25% to 30% of fat calories from absorption.^11,12 During initial clinical trials, patients saw a mean weight loss of 10.2% [10.3 kg] with Orlistat and 6.1% [6.1 kg] with placebo; least squares mean difference 3.9 kg [P < .001] at 1 year in a European multicenter trial¹³ and 8.76 ± 0.37 kg with Orlistat and 5.81 ± 0.67 kg with placebo (P < .001) in a US multi-center trial.¹¹ Subsequently the XENDOS trial saw 73% and 41% of study participants experiencing at least 5% and 10% TBWL, respectively.¹² The mechanism of action makes this medication relatively safe, however, its AEs include significant steatorrhea and fecal urgency with rates ranging from 15% to 30%.¹⁴ Although this can be mitigated by avoiding high-fat diets, the gastrointestinal adverse effects are a common reason for discontinuation.¹⁵ Serious Adverse Event are rare, but have been reported and include liver failure, pancreatitis and renal failure.¹⁵

Second Generation AOMs

Phentermine/Topiramate

The dual drug with phentermine and topiramate (Qsymia, Vivus, Campbell, CA) came to market in 2012. Topiramate was originally designed as an anti-epileptic drug in 1996 and its weight loss effects were incidentally noted. The mechanism of action of how it promotes weight loss is not well understood, however, it is theorized that it leads to appetite suppression by increasing dopamine release, inhibiting glutamate receptors, and modulating neuropeptide Y, a polypeptide involved in metabolic hormone signaling.^16,17 In combination with phentermine, topiramate both has its own appetite suppression and augments the appetite suppression provided by phentermine. In the CONQUER trial participants saw significant weight loss on both the low-dose (phentermine 7.5 mg—topiramate ER 46 mg, N = 498) and high-dose (phentermine 15 mg—topiramate ER 92 mg, n = 995) compared with placebo (n = 994). Patients taking the high dose formulation saw the most significant weight loss with a 10.2 kg mean weight loss compared with 1.4 kg in the control arm at 56 weeks, P < .0001. 70% and 48% of participants in the high dose arm achieved 5% and 10% TBWL, respectively.¹⁸ Rates of AEs in the trial were also dose dependent. In the high dose cohort (16/92 mg), participants most commonly reported xerostomia (21%), constipation (17%) and a small increase in heart rate of 1.6 beats/minute higher than placebo. Mood disturbances including anxiety, depression, and cognitive impairment, seen with phentermine monotherapy were also noted to be increased in a dose dependent fashion.

Bupropion/Naltrexone

The combination of naltrexone with bupropion (Contrave, Orexigan, La Jolla, CA) was approved in 2014. Bupropion inhibits norepinephrine and dopamine reuptake resulting in stimulation of pro-opiomelanocortin neurons (POMC) resulting in increased energy expenditure and decreased food intake. Naltrexone does not appear to have independent metabolic effects, but rather potentiates bupropion by diminishing feedback inhibition of the POMC neurons that bupropion acts on.⁷ In the COR-II trial, participants in the treatment arm loss who completed 56 weeks lost −8.2% TBW compared with −1.4% in placebo; P < .001 with 65% and 39% achieving 5% and 10% TBWL after 1 year.¹⁹ Significant AEs included nausea (30%), constipation (15%), headache (14%).

Liraglutide

Initially approved for the treatment of diabetes in 2010, liraglutide was the first glucagon-like peptide-1 receptor agonist (GLP-1 RA, (Saxenda, Novo Nordisk, Bagsværd, Denmark) approved for weight loss in adults without diabetes in 2014. This class of medications is often now the first agent of choice when pursuing medical weight loss therapy given their effectiveness and benefits in cardiovascular and renal disease, however liraglutide is not as effective as the third generation medications discussed below. GLP-1 RAs promote weight loss mainly by slowing gastric emptying and stimulating POMC neurons which causes satiety.⁷ In the SCALE trial, 3731 patients randomized to either liraglutide or placebo saw a mean 1-year weight loss of 8.4 ± 7.3 kg and 2.8 ± 6.5 kg (P < .001), respectively; with 63% and 33% of patients in the liraglutide arm achieving 5% and 10% TBWL.²⁰ Significant AE were nausea (40%), vomiting (16%), diarrhea (20%), constipation (20%). Serious Adverse Events (SAE) occurred in 6.2% of the liraglutide patients and 5.0% of the control patients, however, gall bladder related events and pancreatitis occurred more often in the liraglutide group (2.5% and 0.4%, respectively).

Third Generation AOMs

Semaglutide

Semaglutide (Wegovy, Novo Nordisk, Bagsværd, Denmark), is a GLP-1 RA with more weight loss potency than liraglutide and approved for obesity treatment in 2021. Data from the modified intention to treat (mITT) population of the STEP-1 trial demonstrated mean 1-year weight loss of 14.9% in the semaglutide arm compared with 2.4% in the placebo arm, P < .001. In this trial 86% and 69% of study participants achieved 5% and 10% TBWL, respectively.²¹ This medication provided substantially more weight loss than previously approved AOMs. Subsequent data from the STEP 3, STEP 4, STEP 5, and STEP 8 trials supported data from the STEP 1 Trial with 15.2% to 17.4% TBWL at 68 weeks to 2 years.^22-25

Further studies supported the use of semaglutide to treat cardiovascular disease and MASH. The SELECT Trial randomized 17 604 patients with pre-existing cardiovascular disease and a BMI of at least 27 kg/m² to 2.4 mg of semaglutide compared with placebo and found that the composite endpoint of death from cardiovascular disease, nonfatal myocardial infarction or stroke occurred in fewer patients treated with semaglutide at 48 months (hazard ratio, 0.80; 95% confidence interval [CI], 0.72 to 0.90; P < .001).²⁶ The ESSENCE Trial randomized 197 patients with biopsy-proven MASH and fibrosis stage of 2 or 3 to 2.4 mg of semaglutide compared with placebo and found resolution of steatohepatitis without worsening of fibrosis in 62.9% and 34.3% of semaglutide and placebo treated patients, respectively (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P < .001) and a reduction in fibrosis without worsening of steatohepatitis in 36.8% and 22.4% of semaglutide and placebo treated patients, respectively (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P < .001).²⁷ These trials led to the approval of semaglutide for the treatment of patients with obesity and cardiovascular disease and patients with obesity and MASH with stage 2 or 3 fibrosis.

Adverse events were commonly seen in the STEP 1 to 3 trials, with gastrointestinal side effects being common and a composite of gastrointestinal disorders occurred in 72.9% of patients on semaglutide and 47.1% of patients in the control arms of the STEP 1 to 3 trials.²⁸ However, these side effects do improve over time and by the time of randomization at 20 week of continued semaglutide or placebo in the STEP-4 trial, only 41.9% of patients randomized to continue semaglutide had GI adverse events.²⁸ Other notable adverse events included gall bladder related disorders 2.6% and acute pancreatitis in 0.2%.²¹ Less common non-GI adverse events that were not elevated compared to the control arm in the STEP 1 trial include psychiatric disorders and acute renal failure.

Tirzapetide

Tirzapetide (ZepBound, Eli Lilly, Indianapolis, IN) is the most recent drug to be approved for weight loss on November 8, 2023. It is a dual GLP-1 RA as well as a glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA). Abundant in adipose tissue, GIP enhances both post-prandial lipid-buffering capacity of white adipose tissue and the sensitivity of these tissues to insulin, possibly preventing ectopic fat deposition.²⁹ It is believed GIP may also have a synergistic effect on GLP-1’s centrally acting impact on satiety and hunger and likely has a more potent central nervous system effect.³⁰ SURMOUNT-1 participants in the mITT population saw a mean weight loss among study participants of 20.9% on the tirzapetide 15 mg dose compared with 3.1% in the placebo arm, P < .001; with 91% having 5% TBWL and 57% having >20% TBWL.³¹ AEs in the study were similar to GLP-1 RA monotherapy including diarrhea (22%) nausea (22%), vomiting (13%), constipation (9%), dyspepsia (7%), and abdominal pain (7%). Only four cases of pancreatitis occurred in this trial, and they were equally distributed among the treatment groups including the control group. These data were supported by later trials in patients with obesity.^32,33

Additionally, the SURMOUNT-OSA study randomized patients with moderate OSA and obesity either not being treated with positive airway pressure (trial 1, n = 469) or currently receiving treatment with positive airway pressure (trial 2, n = 235). The apnea-hypopnea index (AHI) reduced by −25.3 events per hour (95% confidence interval [CI], −29.3 to −21.2) and −5.3 events per hour (95% CI, −9.4 to −1.1) with tirzepatide and placebo (difference of −20.0 events per hour, 95% CI, −25.8 to −14.2, P < .001) in trial 1 and in trial 2, AHI reduced by −29.3 events per hour (95% CI, −33.2 to −25.4) and −5.5 events per hour (95% CI, −9.9 to −1.2) with tirzepatide and placebo, respectively (difference of −23.8 events per hour (95% CI, −29.6 to −17.9), (P < .001).³⁴

The Effect of Anti-Obesity Medications on Gastric Motility

Physiological Studies of Anti-Obesity Medications

As outlined above, several of the anti-obesity medications have effects on gastric motility, with the most notable being GLP-1 RA. However, multiple anti-obesity medications have effects on GI tract motility including orlistat and bupropion/naltrexone. It is well known that orlistat is associated with multiple GI side effects due which include diarrhea, fecal urgency, flatulence, abdominal pain, and rarely pancreatitis and severe hepatocellular injury.³⁵ Orlistat has been shown to increase the rate of gastric emptying. In a cross-over study including patients with type 2 diabetes, total gastric emptying of a solid meal was 61 ± 8 min compared with 98 ± 5 min for meals with pre-treatment of 120 mg of orlistat compared with no orlistat.³⁶ Similar increased rates of emptying were seen in a cross-over study of patients with diabetes consuming a liquid meal.³⁷ Increased rates of gastric emptying have also been seen in non-diabetic healthy male volunteers with a solid mixed meal.³⁸ This study also investigated the effects on gut hormones including cholecystokinin, pancreatic polypeptide, peptide YY and GIP. Treatment with Orlistat significantly decreased the secretion of GIP but did not affect secretion of any of the other gastric peptides. The reduction in GIP, which is known to slow gastric emptying, may explain the increase in gastric emptying with Orlistat treatment.

Bupropion/Naltrexone has been associated with nausea and vomiting in up to 33% and 11% of patients and constipation in 19%.³⁹ Inhibition of gastric mu-opioid receptors has been shown to decrease gastric accommodation during a meal,⁴⁰ which may help to explain nausea and vomiting with this medication. However, it is unclear if bupropion/naltrexone alters gastric emptying.

Physiologic GLP-1 is known to inhibit gastric emptying in humans.⁴¹ Early studies on the effect of synthetic GLP-1 demonstrated antro-duodenal contractility inhibition, stimulation of tonic and phasic pyloric contractions,⁴² increased fundic relaxation, and increased gastric compliance without an increase in sensation of the larger volume.⁴³ Several studies have evaluated gastric emptying in patients treated with GLP-1 RA in patients with obesity. In a study using transit of capsule endoscopy to evaluate rates of motility in patients with diabetes, patients without diabetic neuropathy demonstrated a significant increase in the gastric transit time from 1:01:30 ± 0:52:59 hours before treatment with liraglutide to 2:33:29 ± 1:37:24 hours after treatment (P = .03).⁴⁴ A randomized controlled trial of 136 patients with obesity evaluating gastric emptying with scintigraphy with a radiolabeled solid meal, the active arm treated liraglutide 3.0 mg also found an increase in gastric emptying T_1/2 from 117.2 minutes at baseline to 191.6 minutes at 5 weeks and 154.4 minutes at week 16 after starting liraglutide⁴⁵ and weight loss was associated with the delay in gastric emptying T_1/2.⁴⁶ However, in a follow-up post-hoc analysis, of the 57% of patients who developed a significant delay in gastric emptying at 5 weeks, roughly half had returned to normal by 16 weeks, indicating significant tachyphylaxis.⁴⁷ Gastric emptying evaluated by acetaminophen absorption method in n = 49 patients with obesity and without diabetes in an incomplete cross-over design demonstrated 23% lower gastric emptying at 1-hr in patients treated with liraglutide 3.0 mg compared to the placebo arm (P = .007), but no difference from placebo over the entire 5-hour study.⁴⁸

Similar findings have been seen for both semaglutide and tirzepatide. A single-blind placebo-controlled trial in 20 women with polycystic ovarian syndrome and obesity treated with semaglutide 1.0 mg compared with placebo demonstrated 37% gastric retention in patients treated with semaglutide compared to no gastric retention in patients on placebo at 4 hours using gastric emptying scintigraphy (P = .002).⁴⁹ However, two studies have evaluated the effect semaglutide on gastric emptying using acetaminophen absorption test but did not find significant delayed gastric emptying across the entire gastric emptying study. First hour gastric emptying was delayed in one trial randomized controlled trial with semaglutide 1.0 mg in the active arm compared to placebo control, but no difference was seen in the area under the curve from 0 to 5 hours.⁵⁰ In a randomized controlled trial using semaglutide 2.4 mg in the active arm compared to placebo control there was no evidence of delayed gastric emptying at 20 weeks.⁵¹ One study has evaluated acetaminophen absorption in patients with diabetes and obesity (N = 53) and without diabetes or obesity (N = 33) diabetes treated with ascending doses of tirzepatide. No delay in gastric emptying was seen at tirzepatide 0.5 mg or 1.5 mg once a week, but the time to maximal acetaminophen concentration increased by 1 hour in patients treated with tirzepatide 4.5 mg or 5 mg once a week.⁵²

While considerable variability in these studies exist, a recent meta-analysis of 15 studies, five studies evaluating T_1/2 using scintigraphy in 247 patients found a pooled mean difference of 36.0 minutes (95% CI: 17.0-55.0, I² = 79.4%, Q-value = 19.4, P < .01 in GLP-1 RA users compared to a control group. No significant difference was seen when using acetaminophen absorption test.⁵³

Taken together, most but not all studies evaluating gastric emptying in patients on GLP-1 RA demonstrated delay in gastric emptying, and this may be dose dependent. However, tachyphylaxis and return to normal gastric emptying rate occurs in up to half of patients with delayed gastric emptying at the start of GLP-1 RA use.

Impact of GLP-1 RA Use on Residual Gastric Contents and Adverse Events During Gastrointestinal Endoscopic Procedures

Several studies have now evaluated gastric contents in patients treated with GLP-1 RA. A recent study used ultrasound to evaluate residual gastric volumes in n = 10 patients on semglutide and n = 10 patients not on semaglutide. In the lateral position, solids were present in 90% of semaglutide patients and 20% of control patients. 2 hours after drinking clear liquids, 30% of semaglutide of patients had cleared all solids and 90% of controls had cleared all solids.⁵⁴ However, the control and semaglutide groups were not matched on age or BMI with the semaglutide group being both older and with a higher BMI than the control group.

Multiple studies have evaluated gastric contents during upper endoscopy and the effect of these residual gastric contents (RGC) on aspiration events and failed endoscopy. No randomized controlled trials have been conducted on this topic, but a recent meta-analysis was published which included twenty-three observational case-cohort and case-control studies with 262,018 patients.⁵⁵ Twenty of these studies reported on RGC with a high risk in patients on GLP-1 RA compared with no GLP-1 RA use (7% vs 0.53%; OR, 4.54; 95% CI, 3.30-6.24; P < .00001, I² = 68%), however there was a significant protection against RGC in patients who had both an EGD and colonoscopy on the same day (OR, 0.28; 95% CI, 0.22-0.36; P < .00001, I² = 0%). Early termination of the procedure occurred in more patients on GLP-1 RA (1.26% vs 0.15%; OR, 4.54; 95% CI, 3.05-6.75; P < .00001, I² = 0%), but the rate overall was small for both GLP-1 RA users and non-users. Moreover, there was no difference in the rate of aspiration pneumonia or pneumonitis between GLP-1 RA users and non-users (0.19% vs 0.19%; OR, 0.96; 95% CI, 0.53-1.75; P = .90, I² = 70%). This finding was consistent in sub-group analysis across small and large trials.⁵⁵ An additional analysis of 815 patients published in 2025 evaluated patients who did not stop GLP-1 RA therapy (n = 409) compared to patients who held their GLP-1 RA per the 2023 American Society of Anesthesiologists (ASA) guidance (see below for details, N = 406) demonstrated reduced gastric contents in patients who had held their GLP-1 RA (4.4% and 12.7%, respectively, P < .001), but there was no difference in need for intubation (0% and 2%, respectively P = .53) or aborting the procedure (28% and 18% P = .40).⁵⁶ Only one study performed a subgroup analysis comparing patients with GLP-1 RA users with type 2 diabetes and without type 2 diabetes and found a similar rate of RGC (14% and 11%, P = .64).⁵⁷

In summary, the data suggests that multiple factors influence residual gastric contents, with clear liquids and prep the day before protective against residual gastric contents even in patients who did not stop GLP-1 RA therapy. While adverse events in patients with residual contents were low, procedures were aborted in relatively high percentage of cases and still occurred in patients who had stopped their GLP-1 RA therapy per ASA 2023 guidance, albeit at a lower rate.

Perioperative Considerations Related to Delayed Gastric Emptying in Patients on GLP-1 RA

Although GLP-1 RA have been in use in the US for almost 20 years, the ASA published a consensus-based guidance regarding management of patients on GLP 1 RA undergoing anesthesia for a surgery or procedure in 2023.⁵⁸ As liraglutide has a half-life of 13 hours,⁵⁹ semaglutide has a half-life of 7 days⁶⁰ and tirzepatide has a half-life of 5 days,⁶¹ the authors suggested holding GLP-1 RA medications based on their dosing interval (the day before the procedure for daily injections and 1 week for weekly injections). This is based on gastric emptying data and data regarding residual gastric contents at the time of endoscopy, however they acknowledge that data on the risk of aspiration available at the time was very limited with only a few published case reports. Another limitation of these recommendations is the duration of the effect of GLP-1 RA. The data on residual gastric contents which demonstrated a reduction but not an elimination of risk of residual gastric contents, was not yet published. Moreover, stopping these medications for greater periods of time may have serious negative health consequences.

In response to the ASA guidance, a statement was released by the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), the American College of Gastroenterology (ACG), the American Association for the Study of Liver Disease (AASLD), and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) suggesting physicians use best practices when performing procedures in patients on GLP-1 RA, but that more data was needed before making recommendations regarding holding these medications prior to procedures.⁶² This was followed by a rapid clinical practice management update by the AGA.⁶³ The clinical practice update acknowledges the effect of GLP-1 RA on gastric emptying but addressed the limited data on aspiration risk. They also identified multiple other scenarios with increased risk of gastric contents due to delayed gastric emptying including patients with gastroparesis and patients taking opioid medications. Moreover, as outlined in the section above, newer data demonstrates that stopping GLP-1 RA per the 2023 ASA guidance does not completely ameliorate the risk of residual gastric contents because of the long half-life of the drugs.

In order to come to a consensus with respect to pre-procedure guidance, a multi-society group including the AGA, the American Society for Metabolic and Bariatric Surgeons (ASMBS), the ASA, the International Society of Perioperative Care of Patients with Obesity and the Society of American Gastrointestinal Endoscopic Surgeons published a joint clinical practice guidance document on the safe use of GLP-1 RA in the perioperative period.⁶⁴ This guidance focused on individual patient risk and developing multidisciplinary protocols and procedures for individual practices. Moreover, it was recommended that GLP-1 RA may safely be used in the perioperative period with modifying the preoperative diet to a liquid diet for 24 hours pre-procedure and/or performing point of care ultrasound to assess for retained gastric contents when clinical concern exists and if confirmed, consider/discuss with the patient the risks and benefits of general anesthesia with rapid sequence induction for tracheal intubation.

Conclusion

AOMs are an important arm in the treatment paradigm for patients with obesity. Semaglutide and tirzepatide are significantly more effective than older medications and have been approved to also treat obesity related diseases including diabetes, cardiovascular disease, obstructive sleep apnea and MASLD. Multiple AOMs can alter gut motility. While it is clear that most patients treated with GLP-1 RA will have delayed gastric emptying particularly in the first few months after starting therapy, this has not resulted in a significant increase in aspiration events during endoscopic procedures. Moreover, due to the long half-life of semaglutide and tirzepatide, stopping the last dose of the medication does not appear to completely reverse the effects on gastric emptying while cessation for longer periods may have detrimental effects on patient care. Medical societies have now recommended several approaches to managing patients on GLP-1 RA who are undergoing endoscopic procedures. Individual endoscopy labs are encouraged to develop pre-procedure management protocols that meet the needs to of the endoscopy lab and keep patients on GLP-1 RA safe during endoscopy.

Footnotes

Acknowledgements

No acknowledgements are necessary for this manuscript.

Abbreviations

AOM: anti-obesity medication

MASLD: metabolic dysfunction associated liver disease

GLP-1RA: glucagon-like peptide-1 receptor agonist

GIP-RA: glucose-dependent insulinotropic polypeptide receptor agonist

TBWL: total body weight loss

MASH: metabolic dysfunction associated steatohepatitis

OSA: obstructive sleep apnea

AE: adverse events

POMC: pro-opiomelanocortin neurons

SAE: serious adverse events

mITT: modified intention to treat

AHI: apnea-hypopnea index

RGC: residual gastric contents

ASA: American Society of Anesthesiologists

AGA: American Gastroenterological Association

ASGE: American Society for Gastrointestinal Endoscopy

ACG: American College of Gastroenterology

AASLD: American Association for the Study of Liver Disease

NASPGHN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

ASMBS: American Society for Metabolic and Bariatric Surgeons

OR: odds ratio

ORCID iD

Shelby Sullivan

Ethical Considerations

Ethical approval is not required for this manuscript.

Author Contributions

J. Alexander Torres, MD and Shelby Sullivan, MD contributed equally to this work.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shelby Sullivan: Contracted Research: Allurion (completed), Fractyl Health (ongoing), Viking Therapeutics (ongoing). Consulting: Allurion (completed), Biolinq (ongoing), Fractyl Health (completed), Olympus (ongoing), Pentax (Completed), Stearis (ongoing). Stock: Biolinq. J. Alexander Torres: no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Use of Artificial Intelligence

No artificial intelligence (AI) was used in the preparation of this manuscript.

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