Special report and review

Integrated Upper Gastrointestinal Response to Food Intake

Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC.

Single-center retrospective electronic chart review.

Tertiary hospital.

Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021–March/2022.

Patients were divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy.

Increased RGC was defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content.

Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p < 0.001). Semaglutide use [5.15 (95%CI 1.92–12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2–5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16–0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5 ± 5.5 and 10.2 ± 5.6 days, respectively (p = 0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p = 0.99). Only one case (in the SG) of pulmonary aspiration was reported.

Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC.

Diet modification for heartburn and GERD may vary depending on the severity of symptoms, and focus around trying to decrease pressure and irritation on the lower esophageal sphincter (LES). There is often an overlap with functional bowel disorders. The general diet for heartburn and GERD is very similar to a general diet for irritable bowel syndrome (addressed below). One of the most important factors to discuss with patients is their daily meal intake. Ideally, there should be smaller meals, 4–5 per day, evenly spaced out. Larger meals will place more pressure on the LES, weakening it over time.¹ There is an association between a low number of meals (1–2 per day) and symptoms of GERD.2, 3, 4. Timing of meals in relation to sleep is important to reduce LES pressure. Avoid eating 2–3 h before bed or lying down directly after meals.¹ Patients should notice potential irritating triggers and reduce them. Acidic foods such as coffee, tea, tomato, citrus, vinegar, and spicy foods can irritate. Preliminary studies point to a potential link between certain fermentable carbohydrates (fructans) and relaxation of the LES.⁵ The most common triggers are garlic and onion. There is also a link between prolonged use of proton pump inhibitors and the development of small intestinal bacterial overgrowth (SIBO). When SIBO is present the gas production from high FODMAP foods can exacerbate GERD symptoms and patients have a hard time finding relief. If general diet recommendations do not seem to work with patients, explore options to address potentially linked functional bowel disorders. See function bowel disorders for more information on FODMAPs.

In this study, the effect of emulsifier type, i.e. whey protein versus Tween 80, on the digestion behaviour of emulsion gels containing capsaicinoids (CAPs) was examined. The results indicate that the CAP-loaded Tween 80 emulsion gel was emptied out significantly faster during gastric digestion than the CAP-loaded whey protein emulsion gel. The Tween-80-coated oil droplets appeared to be in a flocculated state in the emulsion gel, had no interactions with the protein matrix and were easily released from the protein matrix during gastric digestion. The whey-protein-coated oil droplets showed strong interactions with the protein matrix, and the presence of thick protein layer around the oil droplets protected their liberation during gastric digestion. During intestinal digestion, the CAP-loaded Tween 80 emulsion gel had a lower extent of lipolysis than the CAP-loaded whey protein emulsion gel, probably because the interfacial layer formed by Tween 80 was resistance to displacement by bile salts, and/or because Tween 80 formed interfacial complexes with bile salts/lipolytic enzymes. Because of the softer structure of the CAP-loaded Tween 80 emulsion gel, the gel particles were broken down much faster and the oil droplets were liberated from the protein matrix more readily than for the CAP-loaded whey protein emulsion gel during intestinal digestion; this promoted the release of CAP molecules from the gel. In addition, the Tween 80 molecules displaced from the interface would participate in the formation of mixed micelles and would help to solubilize the released CAP molecules, leading to improved bioaccessibility of CAP. Information obtained from this study could be useful in designing functional foods for the delivery of lipophilic bioactive compounds.

Few studies have evaluated differences in the curd-forming ability of casein on gastric volume and content directly after ingestion in humans.

This study evaluated the time course of gastric volume and curd conditions in the stomach after protein ingestion.

This was an open-labeled, randomized crossover trial. Ten healthy men [age: 33.4 ± 7.3 y; BMI (kg/m²): 21.9 ± 0.9] received 350 g of 3 isonitrogenous and isocaloric protein drinks containing 30 g micellar casein (MCN), sodium caseinate (SCN), or whey protein concentrate (WPC). The gastric antrum cross-sectional area (CSA) and curd in the stomach were measured using ultrasonography within 5 h after ingestion. The differences between test foods were tested using the MIXED model and post hoc tests using Fisher’s protected least significant difference.

The incremental AUC of the gastric antrum CSA after MCN ingestion was 1.3-fold and 1.5-fold higher than that after the ingestion of SCN and WPC, respectively (both P < 0.05), but not different between SCN and WPC. The number of participants with curds ≥20 mm with a high echogenicity clot observed in the stomach within 5 h after MCN ingestion was significantly greater than that after the ingestion of other proteins (n = 9 for MCN, n = 2 for SCN, and n = 0 for WPC; bothP < 0.01). The regression line slopes on total plasma amino acid concentration and gastric antrum CSA were significantly different between the participants with and without curds.

In contrast to SCN and WPC, MCN ingestion resulted in slow kinetics of gastric antrum CSA. Differences in curd formation of casein in the stomach affect gastric emptying and plasma amino acid absorption kinetics after ingestion in healthy men. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry as UMIN000038388 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043746).

Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D.

Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons.

Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, −1.30% [95%CI: -1.44, −1.16], P < 0.05) and body weight (MD, −3.17 kg [95%CI: -3.89, −2.45], P < 0.05) compared to placebo (MD, HbA1c: -0.32% [95%CI: -0.49, −0.15], P < 0.05; MD body weight: -2.56 kg [95%CI: -3.41, −1.71], P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD: -0.26% [95%CI: -0.44, −0.07], P < 0.05) and body weight (MD: -1.08 kg [95%CI: -2.04, −0.12], P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide.

Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.

A dynamic in vitro human stomach (DIVHS), simulating the anatomical structures, peristalsis, and biochemical environments of a real stomach as practically as possible, was applied to mimic the gastric pH and emptying during yogurt digestion in short/long gastric residence times. The influences of peristalsis, dilution, and proteolysis on digesta viscosity were quantified respectively, indicating the dominant role of proteolysis and dilution. After incorporating curcumin-whey protein microparticles with targeted-release formula in yogurt, the peak curcumin release during intestinal digestion reached 43% at 120 min in the short gastric residence time and 16% at 180 min in the long gastric residence time. The change in the maximum curcumin release depended on the gastric emptying kinetics in each residence time. This emptying-kinetics dependence was reflected by the slower microparticle disintegration and proteolysis in the long gastric residence time. The dynamic reproduction of realistic gastric conditions using DIVHS helps revealing controlled release from foods.