Gastric residual volume in patients with obesity receiving GLP-1 receptor agonists: A comparative gastric ultrasound pilot study

Abstract

Background:

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) enhance insulin secretion, suppress glucagon release, promote satiety, and may slow gastric emptying. Introduced in 2005 for the treatment of type 2 diabetes and obesity, these agents have prompted interest in assessing delayed gastric emptying as a potential biomarker to predict treatment response and to guide decisions regarding long-term therapy. Point-of-care gastric ultrasound (POCUS) offers a bedside method to assess gastric contents.

Objectives:

To compare gastric residual volume (GRV) on gastric ultrasound among patients with obesity receiving GLP-1 RAs and nonusers and those with prior weight loss surgeries.

Methods:

In this comparative cross-sectional pilot study, gastric POCUS was done on patients with obesity who took GLP-1 RAs and other patients with obesity with no history of taking GLP-1 RAs prior to surgery in the supine and lateral decubitus positions. Antral cross-sectional area and GRV were measured using validated mathematical models.

Results:

Patients receiving GLP-1 RAs demonstrated higher estimated GRV compared with nonusers. A higher proportion of GLP-1 RA users met ultrasound criteria for a full stomach.

Conclusion:

Among patients with obesity, GLP-1 RA therapy was associated with enlargement of the gastric antrum, increased gastric volume, and greater residual gastric contents, leading to an elevated estimated risk of aspiration. This increased risk is primarily determined by gastric ultrasound findings rather than patient characteristics, comorbidities, or duration of treatment. Gastric ultrasound may support individualized perioperative decision-making regarding aspiration precautions.

Introduction

Over the past 30 years, Saudi Arabia has seen a steady rise in obesity rates. Obesity is a major contributor to noncommunicable diseases, leading to substantial healthcare and economic challenges. Recent estimates show that obesity affects between 20% and 39% of adults and up to 19.4% of adolescents in the country. Overall, the financial impact of obesity on the nation’s healthcare system is significant, amounting to approximately 6.4 billion USD in treatment and management costs.[1]

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more important in treating type 2 diabetes (T2D) and obesity. In addition to their strong glucose-lowering properties, GLP-1 RAs contribute to weight loss in individuals with obesity, lower the risk of cardiovascular and kidney disease, and may help improve metabolic dysfunction-associated steatotic liver disease. These agents influence gastric, intestinal, and gallbladder motility, which can have therapeutic benefits such as delaying the absorption of glucose and fats after eating but may also pose risks.[2]

Potential adverse effects include nausea, diarrhea, and vomiting in addition to the retention of gastric contents, which could lead to pulmonary aspiration during procedures like endoscopy or when general anesthesia is administered, as well as complications involving the gallbladder and biliary system.[3] This risk is increased by factors such as a full stomach, impaired airway protection reflexes, and decreased levels of consciousness. Patients taking GLP-1 RA medications may be at greater risk compared to the general population as these drugs can delay gastric emptying, potentially leading to retained stomach contents during anesthesia.[4] Despite growing clinical recognition of this issue, the extent of gastric retention and its implications for anesthetic management remain insufficiently characterized.

Recent research has reported that patients treated with GLP-1 RAs showed significantly higher gastric residue on upper endoscopy compared with matched controls, with particularly elevated rates among insulin-dependent type 2 diabetics and those with diabetes-related complications. These findings were attributed to the fact that GLP-1 RAs induced delayed gastric emptying.[5] Similarly, Sen et al.[6] observed that 56% of patients on GLP-1 RA therapy had increased residual gastric content, compared with 19% in the control group; after adjusting for confounders, GLP-1 RA use remained strongly associated with elevated residual gastric content, showing a 30.5% higher incidence and an adjusted prevalence ratio of 2.48.

Collectively, these observations underscore the need for further investigation into the clinical implications of GLP-1 RAs-associated gastric retention, particularly in high-risk patient populations. In addition to this, the American Society of Anesthesiologists (ASA) has recently issued consensus-based recommendations to address the potential aspiration risk associated with GLP-1 RA use; however, these guidelines are primarily grounded in expert opinion due to the paucity of supporting evidence, highlighting an urgent need for additional data.[7]

The aim of this pilot study was to assess gastric residual volume (GRV) in patients with obesity by comparing those treated with GLP-1 RAs to untreated patients and to evaluate the association between GRV and relevant clinical and demographic factors in patients with obesity receiving GLP-1 RA therapy.

Methods

This comparative cross-sectional pilot study was approved by the Institutional Review Board of King Saud University (IRB Approval of Research Project No. E-25-10290: November 2025). Written informed consent was obtained from all participants in accordance with the principles of the Declaration of Helsinki. Participants were informed about the purpose and procedures of the study and were assured of the confidentiality of their data. Only patients who provided informed consent were included in the study. Ethics committee approval was obtained. Date of Approval: 19 November 2025. Reference No.: 25/0875/1RB. IRB No.: E-25-10290.

A total of 30 patients aged over 18 years with obesity (body mass index [BMI] >35 kg/m²), of both sexes, and scheduled for elective weight loss surgery were included. Patients were excluded if they had medical comorbidities (e.g., diabetes mellitus, hypertension, or renal disease), were receiving daily oral or injectable GLP-1 RAs, or were unable to recall the timing of their last dose of GLP-1 RAs.

The patients were divided into two groups (each 15). The case group included patients with obesity who had received GLP-1 RAs within 7 days prior to gastric point-of-care ultrasound (POCUS), while the control group included patients with obesity scheduled for surgery (sleeve) with no history of GLP-1 RA use.

Data collection

Demographic data (age, sex), preoperative BMI, duration of taking, dose of GLP-1 RAs, type of surgery, and past medical and operative history were recorded.

Study procedures

Gastric ultrasound examinations were performed using a low-frequency (2–5 MHz) curved array transducer (SonoSite X-Porte, Fujifilm Sonosite, Inc., Bothell, WA) oriented in the parasagittal plane. Patients were scanned in both the supine and right lateral decubitus (RLD) positions. The ultrasound settings were adjusted to clearly visualize the abdominal aorta, with the probe placed just below the xiphoid process and oriented perpendicular to the abdomen, angled cephalad. During the procedure, key anatomical landmarks including the stomach, liver, aorta, superior mesenteric artery, and pancreas were identified. Gastric contents were assessed with the patient presented in supine position, followed by evaluation in the RLD position.

A stomach is considered “full” if solid matter or thick fluid is present in either position or if clear liquid is detected with a cross-sectional area (CSA) exceeding accepted risk thresholds (greater than 10 cm² or an estimated gastric volume exceeding 1.5 mL/kg in the RLD position). Conversely, an “empty stomach” is characterized by a bullseye or donut-shaped appearance in RLD, or clear fluid with a CSA below 10 cm² or a volume equal to or less than 1.5 mL/kg. All ultrasound assessments were conducted and interpreted by anesthesiologists with advanced training and experience in POCUS techniques.

The estimated GRV (in mL) for adults can be calculated using a validated formula based on the antral CSA measured in the right lateral decubitus position.[8]

Gastric Volume (mL) = 27 + (14.6 × CSA in cm²) − (1.28 × Age in years).

Statistical analysis

The data were analyzed using SPSS (Statistical Package for the Social Sciences) version 26.0 and Epi info for windows version 3.5.3. Categorical variables were summarized as frequencies and percentages. Continuous variables were assessed for normality and were expressed as mean and standard deviation as appropriate group comparison was performed using the independent sample t-test or Mann–Whitney tests and Chi-square test or Fisher test for qualitative data. A two-sided P < 0.05 with a 95% confidence interval was considered statistically significant.

Results

This comparative cross-sectional study included 30 patients (15 not received GLP-1 RA group I and 15 received GLP-1 RA II). Regarding age and BMI, Table 1 reveals that there is a statistically significant difference between studied groups. The mean age of Group I (non-GLP-1 RA users) was 31.73 ± 10.9 years, compared with 42.67 ± 8.65 years in Group II (GLP-1 RA users). Additionally, the mean BMI was significantly higher in Group I (50.46 ± 12.74) than in Group II. No statistically significant difference was observed between the two groups regarding sex distribution.

Table 1.

Basic characteristics of the studied groups (n=30)

Variables	Group I (not received GLP-1 RAs) (n=15)	Group II (received GLP-1 RAs) (n=15)	test	P
Age (years):
Mean±SD	31.73±10.9	42.67±8.65	-3.042 (t)	0.005*
BMI
Mean±SD	50.46±12.74	39.11±2.6	3.382 (t)	0.002*
Sex:
Female	NO. (%)	NO. (%)	0.133 (x2)	0.715
Male	7 (46.7%)8 (53.3%)	8 (53.3%)7 (46.7%)

(t) Independent sample t test (x²) Chi-square test, *Indicates statistical significance at P < 0.05

Table 2 shows that there are statistically significant differences observed between the groups in terms of antral CSA measured in the supine position and RLD position, as well as gastric volume (GV). The mean antral CSA in the supine position was significantly greater in Group II (8.1 ± 2.22) compared with Group I (4.35 ± 1.8). Similarly, the mean antral CSA in the RLD position was higher in Group II (8.34 ± 2.2) than in Group I (4.54 ± 1.79). The median GV was also significantly greater in Group II [102 (68–115.5)] compared with Group I [42.3 (37.45–64.45)].

Table 2.

Clinical assessments of the studied groups (n=30)

Variables	Group I (not received GLP-1 RAs) (n=15)	Group II (received GLP-1 RAs) (n=15)	Test	P
Antral CSA-supine (Mean±SD)	4.35±1.8	8.1±2.22	-5.069 (t)	<0.001*
Antral CSA-RLD (Mean±SD)	4.54±1.79	8.34±2.2	-5.165 (t)	<0.001*
GV in ml Median (IQR)	42.3 (37.45-64.45)	102 (68-115.5)	-2.883 (mw)	0.004*

(t) Independent sample t test (mw) Mann–Whitney test, *Indicates statistical significance at P < 0.05

As presented in Table 3, a statistically significant difference in American Society of Anesthesiologists (ASA) physical status classification was observed between the two groups. ASA class II was higher in Group II (GLP-1 RA users), 66.7% of patients, whereas ASA class III was more frequently observed in Group I (non-GLP-1 RA users). No statistically significant difference was identified between the groups with respect to gastric content.

Table 3.

ASA and gastric content among the studied groups (n=30)

Category	Variables	Group I (not received GLP-1 RAs) (n=15)		Group II (received GLP-1 RAs) (n=15)		X 2	P
		N	%	N	%
ASA	II	4	26.7	10	66.7	4.821	0.028*
	III	11	73.3	5	33.3
Gastric content	Normal	15	100	11	73.3	4.615	0.099
	Solid early stage	0	0	1	6.7
	Solid late stage	0	0	3	20

(x²) Chi-square test, *Indicates statistical significance at P < 0.05

Table 4 demonstrates a statistically significant difference in aspiration risk between studied groups. Low aspiration risk was observed in 93.3% of patients in Group I, compared with only 46.7% in Group II.

Table 4.

Risk aspiration among the studied groups (n=30)

Category	Variables	Group I (not received GLP-1 RAs) (n=15)		Group II (received GLP-1 RAs) (n=15)		X 2	P
		n	%	n	%
Risk aspiration	Low	14	93.3	7	46.7	7.778	0.005*
	High	1	6.7	8	53.3

(x²) Chi-square test, *Indicates statistical significance at P < 0.05

Table 5 outlines GLP-1 agonist therapy in Group II, with most patients receiving a 1 mg dose and 13.3% receiving 0.5 mg. The mean duration of therapy was 4.73 ± 1.22 months (range, 2–6 months). As shown in Table 6, aspiration risk within Group II was not significantly associated with age, body mass index, or sex. However, Tables 7 and 8 demonstrate a significant association between aspiration risk and gastric ultrasound parameters, whereby higher antral CSA in both the supine and right lateral decubitus positions, as well as increased GV, and gastric content were associated with a higher aspiration risk, while there is no significant difference in risk aspiration regarding medical history and therapy duration and dose.

Table 5.

Dose and therapy duration in group II (received GLP-1 agonist)

	Category	n	%
Dose	0.5 mg	2	13.3
	1 mg	13	86.7
Duration (months)	Mean±SD	4.73±1.22
	Range	(2-6)

Table 6.

Relation between basic characteristics and risk aspiration in group II (received GLP-1 RAs)

Variables	Risk aspiration		test	P
	Low	High
Age (years):
Mean±SD	43.57±8.67	41.87±9.14	0.367 (t)	0.719
BMI
Mean±SD	38.94±2.33	39.25±2.97	-0.220 (t)	0.829
Sex:		NO. (%)	NO. (%)
Female	4 (57.1%)	4 (50%)	0.077 (x2)	0.782
Male	3 (42.9%)	4 (50%)

(t) Independent sample t test (x²) Chi-square test, significant P<0.05

Table 7.

Relation between clinical assessments and risk aspiration in group II (received GLP-1 RAs)

Variables	Risk aspiration		Test	P
	Low	High
Antral CSA-supine (Mean±SD)	6.55±2.05	9.45±1.34	-3.271 (t)	0.006*
Antral CSA-RLD Mean±SD	6.8±2.04	9.68±1.3	-3.317 (t)	0.006*
GV in ml Median (IQR)	52 (40.6-86.5)	114 (103-129.5)	-2.777 (mw)	0.005*

(t) Independent sample t test (mw) Mann–Whitney test, *Indicates statistical significance at P < 0.05

Table 8.

Relation between medical history, gastric content, dose, and therapy duration with aspiration risk in group II (received GLP-1 RAs)

Variables	Risk aspiration		X 2	P
	Low	High
Medical history	NO. (%)	NO. (%)
HTN	1 (14.3%)	3 (37.5%)	1.272	0.529
MF	6 (85.7%)	5 (62.5%)
Gastric content
No	7 (100%)	4 (50%)	4.773	0.029*
Solid	0 (0%)	4 (50%)
Duration (months)
Mean±SD	4.43±1.397	5±1.069	-0.897 (t)	0.386
Dose:	No %	No %
0.5 mg	2 (28.6%)	0 (0%)	2.637 (x2)	0.104
1 mg	5 (71.4%)	8 (100%)

(t) Independent sample t test (x²) Chi-square test, *Indicates statistical significance at P < 0.05

Discussion

In the current study, significant differences in age and BMI were observed between groups, with GLP-1 RA users being older and having a lower BMI compared with nonusers. These findings likely reflect broader clinical patterns in which GLP-1 RAs are more frequently prescribed to patients with established obesity and associated risk factors, including older age and longer duration of excess weight, rather than to younger individuals with higher baseline BMI. Wong et al.[9] documented that GLP-1 RAs like tirzepatide and semaglutide cause clinically significant drops in body weight and BMI in persons who are overweight or obese, with average BMI drops of at least 2 kg/m² when compared to placebo controls. Because treated patients may have already undergone partial therapeutic weight reduction prior to evaluation, these pharmacologic effects offer a possible explanation for the reduced mean BMI seen in the GLP-1 RA group in the current cohort. GLP-1 RA treatment users frequently differ from nonusers in terms of age, comorbidity profiles, and prevalence of obesity before adjustment, according to observational data from large cohorts.[10]

Our findings demonstrated that patients receiving GLP-1 RAs had significantly larger antral CSAs in both the supine (8.1 ± 2.22 vs. 4.35 ± 1.8 cm²) and right lateral decubitus positions (8.34 ± 2.2 vs. 4.54 ± 1.79 cm²), as well as higher median gastric volumes [102 (68–115.5) mL vs. 42.3 (37.45–64.45) mL] compared with nonusers. These results indicate that GLP-1 therapy is associated with delayed gastric emptying and increased residual gastric content, consistent with the known pharmacodynamic effects of this drug class.

Point-of-care gastric ultrasonography has been used to quantify this effect specifically, and it shows that GLP-1 RA users had higher Perlas grades and bigger residual material than nonusers even following normal fasting intervals.[11]

Our results are in agreement with AbuFreha et al.,[2] who reported GLP-1 RA users had a considerably greater prevalence of gastric residue on upper endoscopy than nonusers (5.6% vs. 2.0%; P < 0.001). By measuring antral CSA and gastric volume using POCUS in a perioperative setting, our study adds to the evidence that GLP-1 RA-associated changes in gastric physiology are detectable even after standardized fasting, whereas their study evaluated residual gastric content during clinically indicated endoscopy.

Our findings were supported by those obtained by Shankar et al.,[4] who examined the relationship between stomach motility and GLP-1 RA signaling. The physiological consequence that underpins both our ultrasonographic data and more general clinical concerns regarding aspiration risk is that GLP-1 RAs decrease stomach emptying by regulation of enteric and vagal pathways, resulting in delayed transit and increased remaining gastric contents. In the context of anesthesia and invasive operations, such as heart surgery, where leftover stomach contents may raise the risk of pulmonary aspiration during anesthesia induction, they talked about the significance of delayed gastric emptying.

In the present study, a statistically significant difference was observed between groups in terms of ASA physical status classification. Patients receiving GLP1 RAs were more frequently classified as ASA II (66.7%), whereas nonusers had a higher proportion of ASA III patients. This distribution likely reflects differences in baseline comorbidities and overall perioperative risk, with GLP1 RA users generally being healthier or having fewer severe systemic diseases at the time of surgery.

The ASA guidelines emphasize that when planning for anesthesia in patients on GLP-1 RAs, clinicians should take into account the possibility of increased residual GV and motility changes. They recommend modified perioperative strategies, such as holding the medication before elective procedures or using gastric ultrasound to assess residual content when appropriate, even though our study did not find a significant difference in gastric content between groups.[7]

In the present study, a statistically significant difference in estimated aspiration risk was observed between the groups. Low aspiration risk was present in 93.3% of non-GLP1 RA users, compared with only 46.7% of GLP1 RA users. This finding aligns with the known pharmacologic effects of GLP1 RAs, which delay gastric emptying and increase GV, thereby potentially elevating the risk of regurgitation and aspiration during anesthesia. Although no difference in solid gastric content was observed between groups, the larger antral cross-sectional area and increased GV detected in GLP1 RA users likely contributed to their higher estimated aspiration risk.

While estimated aspiration risk was elevated among GLP1 RA users, several studies indicated that this physiologic risk does not always translate into clinically significant aspiration events. Chen et al.[12] found that in surgical patients on GLP-1 RA medication, there was no statistically significant increase in postoperative aspiration pneumonia despite delayed stomach emptying. Similarly, Stryelkina et al.[13] showed that even when leftover stomach contents were seen, endoscopic procedures in GLP-1 RA patients did not cause clinically noticeable aspiration episodes. These findings imply that the potential risk of GLP-1 RA-induced gastroparesis may be reduced by preoperative fasting, procedural safety measures, and meticulous anesthetic preparation.

Within the GLP1 RA group (Group II), estimated aspiration risk was not significantly associated with age, BMI, or sex. This suggests that the observed increase in aspiration risk among GLP1 RA users is primarily driven by the pharmacologic effects of the drug on gastric motility and emptying, rather than by patient demographic or anthropometric factors. This suggests that gastric physiology, rather than patient characteristics or cumulative drug exposure, primarily drives aspiration risk which aligns with the mechanistic observations discussed by Jalleh et al.[3] and Li et al.,[14] emphasizing that delayed gastric emptying occurs independently of age, BMI, or sex.

In the present study, a significant association was observed between aspiration risk and gastric ultrasound parameters. Specifically, patients with a higher antral CSA in both supine and right lateral decubitus positions, increased GV, and the presence of gastric content were more likely to be classified as having higher aspiration risk.

Similar findings were obtained by Chaitra et al.,[8] who reported that patients who have greater residual volumes and bigger sonographically assessed antral CSA are more likely to fit the criteria for a “risky stomach” (residual volume >1.5 mL/kg), a categorization associated with a higher risk of aspiration if left untreated. Baldawi et al.[15] stated that the association between ultrasonography indices (CSA and volume) and aspiration risk is further supported by the fact that patient groups with delayed gastric emptying, such as diabetics, have a greater incidence of sonographically characterized high-risk stomachs.

The limitation of our study included being a pilot with a small sample size opt more randomized clinical trials to establish a clinical practice guideline for patients with obesity on GLP-1 RAs undergoing weight loss surgery with aspiration risk.

Conclusion

GLP-1 RA use in patients with obesity is associated with increased antral CSA, GV, and residual gastric content, resulting in a higher estimated aspiration risk. This risk is driven by gastric ultrasound findings rather than patient demographics, medical history, or therapy duration. Point-of-care gastric ultrasound is a valuable tool for individualized preoperative aspiration risk assessment in patients receiving GLP-1 RAs.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.