Dipeptidyl peptidase-4 (DPP-4) is a critical target for the treatment of type 2 diabetes. This study outlines the development of six compounds derived from food sources and modified to create promising candidates for the treatment of diabetes. These compounds were identified through a combination of virtual screening, deep learning algorithms, ADMET characterization assessment, and molecular dynamics simulations. Furthermore, a taste prediction model was used to assess the flavor of these DPP-4 inhibiting compounds. After thorough evaluation, we concluded that the six food-derived DPP-4 inhibitors identified have significant potential for therapeutic success. This study has greatly contributed to the discovery of novel dietary supplements for the management of type 2 diabetes.

Protein tyrosine phosphatase N1 (PTPN1) is a key regulator of insulin and leptin signaling pathways, making it an attractive therapeutic target for type 2 diabetes. Recent studies have identified fatty acid conjugated BimBH3 analogues as promising PTPN1 inhibitors with antidiabetic potential. Peptide therapeutics have proven successful in the treatment of a wide range of medical conditions, yet challenges such as poor aqueous solubility, proteolytic degradation, and limited bioavailability still hinder their clinical application. In this study, we developed a series of novel BimBH3 peptide analogues through dual modifications involving fatty acid lipidation and glycosylation to address these limitations. These modifications significantly improved the peptides' solubility, proteolytic stability, and plasma half-life while preserving potent PTPN1 inhibitory activity, which is essential for enhancing insulin signaling in type 2 diabetes treatment. Among the analogues, compound L3 exhibited the most balanced profile, with an aqueous solubility increase over 10-fold, a half-life extension in rat plasma of 9.92-fold compared to the lead compound, and an IC50 of 0.78 μM against PTPN1. In vivo studies further demonstrated L3's efficacy in lowering blood glucose levels in mice. This study demonstrates the utility of glycosylation in overcoming the solubility and stability challenges associated with lipidated peptides. The optimized analogue L3 could serve as a proof of concept for developing novel long-acting PTPN1 inhibitors.

The perioperative management of patients using glucagon-like peptide 1 receptor agonists remains a topic of debate. While several multisociety statements have been published recently, the recommendations vary significantly in terms of medication management and preoperative fasting protocols for these patients. This document represents a multidisciplinary consensus statement led by the Society for Perioperative Assessment and Quality Improvement (SPAQI). It provides updated recommendations based on a modified Delphi process and supported by a systematic review of the current literature. The recommendations address management of the glucagon-like peptide 1 receptor agonists perioperatively, and preoperative fasting times for both solids and liquids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023438624).

Many studies have shown a close relationship between type 2 diabetes mellitus and obesity. Glucagon-like peptide-1 (GLP-1) agonists are particularly preferred as antidiabetic medications for obese patients with type 2 diabetes because they not only help with glycemic control but also promote weight loss by slowing gastric emptying. Fatty liver disease, a significant complication of obesity, can progress to hepatic fibrosis and cirrhosis in later stages. Platelets ratio index (APRI), fibrosis-4 index (FIB-4), indices are two of the most studied indirect markers of hepatic fibrosis. Our study aimed to investigate the effect of exenatide, a GLP-1 agonist, on the APRI and FIB-4 indices in obese patients with type 2 diabetes mellitus. We included obese patients with type 2 diabetes treated with exenatide at the endocrinology and metabolism outpatient clinics of Bakırköy Dr. Sadi Konuk Training and Research Hospital between January 2015 and May 2018. We calculated the APRI and FIB-4 indexes retrospectively using data on aspartate aminotransferase, alanine aminotransferase, platelet counts, and ages. The study included 170 patients, with an average age of 48.27 ± 11 years. We compared the APRI and FIB-4 indices at the third and sixth months after the onset of exenatide and before the treatment. While there was no significant change in the FIB-4 index with treatment, the APRI index showed a significant decrease. In conclusion, our study observed a significant decrease in the APRI index with exenatide treatment, while the FIB-4 index remained unchanged. More research is needed on liver fibrosis indices in the obese population.

Perioperative management of patients receiving a glucagon-like peptide-1 receptor agonist (GLP-1 RA) remains challenging for the anesthesiologist. Despite the approval of GLP-1 RAs 2 decades ago, the recent reports of aspiration and postoperative pulmonary complications drew attention to this group of medications and resulted in multiple societal guidelines that would provide recommendations for anesthesiologists and proceduralists on the appropriate perioperative management of GLP-1 RAs. However, despite these guidelines and proposed options, there was a lack of adequate evidence to support holding versus continuing the medication, as well as data related to the role of gastric ultrasound in that decision-making process. The release of multiple societal guidelines and studies evaluating the impact of GLP-1 RAs on perioperative outcomes resulted in more controversy and uncertainty for the clinician anesthesiologist to follow. The ultimate goal for perioperative management of these medications is to evaluate an individual patient's risk of aspiration, rather than assuming the risk is low when holding the medication appropriately or high if not holding it. Furthermore, it is unclear whether holding these types of medicines or unnecessary postponing of surgery may result in adverse outcomes. In this narrative review, we present a summary of the existing literature on the topic with a focus on the risk of aspiration and a recommendation for perioperative management to include the utilization of gastric ultrasound for surgery patients based on their risks.

Gastric point-of-care ultrasound (POCUS) may offer clinical value in assessing aspiration risk among medically complex patients undergoing regional anesthesia and pain procedures. While the American Society of Anesthesiologists (ASA) preoperative fasting guidelines primarily apply to healthy individuals, medically complex populations often present with differing gastric emptying and aspiration risk. This narrative review, conducted by the American Society of Regional Anesthesia and Pain Medicine (ASRA-PM), adhered to PRISMA guidelines and was registered with PROSPERO. It focused on seven medically complex patient groups: those who are pregnant, obese, diabetic, have gastroesophageal reflux disease (GERD), are receiving emergency care, are enterally fed, or are taking GLP-1 receptor agonists (GLP-1RA). Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Practice recommendations were developed using an iterative expert consensus process, with final recommendations based on evidence strength, clinical relevance, and expert agreement. Findings support the use of gastric POCUS in patients in active labor, those undergoing urgent cesarean sections, and those with diabetes. Conditional support is given for obesity, emergency care, enteral feeding, and GLP-1RA use. Routine use is not recommended in non-laboring pregnancies, elective cesarean delivery, or GERD. While gastric POCUS may aid with aspiration risk evaluation, its use should complement clinical judgment. Implementation may be limited by practical and training constraints, requiring individualized decision-making. These recommendations serve as a foundation for future research and potential clinical guideline development. PROSPERO registration number: CRD42023445927.

The heterogeneity among patients with obesity is particularly evident in the weight loss response to interventions such as diets, drugs, devices and surgery. Obesity can be "catalogued" into four phenotypes: hungry brain (abnormal satiety for alteration of gut-brain axis), emotional hunger (hedonic eating), hungry gut (abnormal duration of satiety for faster gastric emptying) and slow burning (slowing of the metabolic rate). Phenotypes are grafted onto this complexity, the recognition of which allows for personalized medicine and increasingly targeted therapies. Although there are no standardized treatment protocols, we present management options consisting of lifestyle modifications and pharmacologic therapies. Nutritional advice and encouragement of adequate physical activity lead to increased self-efficacy and promote a sense of well-being when coupled with psychological approaches involving mindful eating. In summary, obesity has a complex pathophysiology best addressed through a therapeutic process suited to the phenotype encountered and in synergy with multifactorial interventions.

The use of glucagon-like peptide 1 receptor agonists has been associated with gastroparesis, but little is known about the risk of gastroparesis in those with obesity but without type 2 diabetes (T2D), and how that risk compares with other treatment modalities for obesity. This study aims to characterise the relationship between different treatment modalities for obesity and the risk of gastroparesis in a population without pre-existing T2D.

A retrospective cohort study using Merative MarketScan Research Databases of individuals with obesity who underwent treatment with semaglutide, bupropion-naltrexone or sleeve gastrectomy from 1 January 2018 to 31 December 2022. The incidence of gastroparesis diagnosis was evaluated using International Classification of Diseases, Version 10 codes. The risk of gastroparesis was compared between three intervention groups using Cox proportional hazards regression models.

Of the 55 460 individuals included, 36 990 (66.7%) were treated with semaglutide, 7369 (13.3%) with bupropion-naltrexone and 11 101 (13.7%) with sleeve gastrectomy. Gastroparesis rates among those treated with semaglutide versus bupropion-naltrexone versus sleeve gastrectomy were 6.5 per 1000 person-years (PY) vs 2.1 per 1000 PY vs 1.1 per 1000 PY, respectively. After adjusting for baseline characteristics, individuals treated with semaglutide had a higher risk of gastroparesis than those treated with bupropion-naltrexone (adjusted HR 3.33, 95% CI 2.27, 4.98) and sleeve gastrectomy (adjusted HR 6.14, 95% CI 3.94, 9.57).

There is an increased incidence of gastroparesis among individuals with obesity without T2D who are using semaglutide as compared with bupropion-naltrexone and sleeve gastrectomy. Understanding these potential side effects, though rare, may help guide personalised treatment regimens.

Glucagon-like peptide-1 receptor agonists, dual glucose-dependent insulinotropic peptide receptor agonists and sodium-glucose cotransporter-2 inhibitors are used increasingly in patients receiving peri-operative care. These drugs may be associated with risks of peri-operative pulmonary aspiration or euglycaemic ketoacidosis. We produced a consensus statement for the peri-operative management of adults taking these drugs.

This multidisciplinary consensus statement included surgeons, anaesthetists, physicians, pharmacists and people with lived experience relevant to these guidelines. Following the directed literature review, a three-round modified Delphi process was conducted to generate and ratify recommendations.

Patients taking glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic peptide receptor agonists should: continue these drugs before surgery; have full risk assessment and stratification; and receive peri-operative techniques that may mitigate risk of pulmonary aspiration before, during and after sedation or general anaesthesia. Patients taking sodium-glucose cotransporter-2 inhibitors should omit them the day before and the day of a procedure. All patients should have risks and mitigation strategies discussed with a shared decision-making approach.

Until more evidence becomes available, this pragmatic, multidisciplinary consensus statement aims to support shared decision-making and improve safety for patients taking glucagon-like peptide-1 receptor agonists, dual glucose-dependent insulinotropic peptide receptor agonists and sodium-glucose cotransporter-2 inhibitors during the peri-operative period.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus and obesity, but safety concerns have been raised for users undergoing GI endoscopy because of retained food and aspiration events. We compared the risk of adverse events for GLP-1RA users and nonusers undergoing endoscopy.

We conducted a systematic review and meta-analysis (PROSPERO registration: CRD42024556732). A systematic search in PubMed, Scopus, Web of Science, and Cochrane Central was performed from their inception until July 1, 2024 (EMBASE from 1974 to June 28, 2024). Double-arm adult human original studies (observational, randomized controlled trial) with a sample size of ≥20 undergoing EGD or endoscopy with no GLP-1RA use in the control arm were searched. Studies were excluded if they were single arm and had any use of GLP-1RA before the procedure in the control arm. Residual gastric contents (RGCs), aspiration pneumonia, and premature endoscopy termination were the main outcomes. The random-effects model was used to pool and get final effect estimates.

Twenty-three observational studies were selected consisting of 262,018 patients. GLP-1RA users had a statistically significant increase in the risk of RGCs (odds ratio [OR], 4.54; 95% confidence interval [CI], 3.30-6.24; P < .00001, I2 = 68%) and premature endoscopy termination (OR, 4.54; 95% CI, 3.05-6.75; P < .00001, I2 = 0%). There was no significant difference in the risk of aspiration pneumonia (OR, .96; 95% CI, .53-1.75; P = .90, I2 = 70%). A significant reduction was seen in RGCs when EGD and colonoscopy (OR, .28; 95% CI, .22-.36; P < .00001, I2 = 0%) were done the same day versus EGD alone.

GLP-1RA use was associated with an increased risk of RGCs and premature endoscopy termination, but no significant difference was found in the risk of aspiration pneumonia in patients undergoing endoscopy.

This analysis evaluated whether gastrointestinal (GI) adverse events (AEs) including nausea, vomiting, diarrhoea (N/V/D) and dyspepsia were associated with weight reduction with tirzepatide across the SURMOUNT-1 to -4 trials.

SURMOUNT-1 to -4 were global Phase 3 clinical trials evaluating the safety and efficacy of tirzepatide among participants with obesity or overweight with or without type 2 diabetes (T2D). Participants were randomly assigned to receive once weekly subcutaneous tirzepatide or placebo. This post hoc analysis investigated weight change at the primary endpoint from baseline among participants who self-reported no N/V/D, any N/V/D or nausea alone. Mediation analyses evaluated the contribution of N/V/D and dyspepsia on weight reduction. Time to first use of antidiarrheal and antiemetic usage was reported by time intervals.

Baseline characteristics were similar between participants who reported N/V/D and those who did not. More participants reported GI AEs in the tirzepatide treatment arms (27.8%-72.8%) than with placebo (12.2%-32.5%). Most GI AEs were non-serious and occurred during dose escalation. Between 1.0% and 10.5% of tirzepatide-treated participants discontinued treatment due to GI AEs. Weight reduction with tirzepatide was similar among participants reporting no nausea, nausea alone, or any N/V/D. Mediation analyses suggested that N/V/D and dyspepsia were associated with up to 3.1% of total weight reduction. When required, first use of antidiarrheal and antiemetic medication was most commonly reported during dose escalation.

In this post hoc analysis, GI AEs appeared to contribute slightly to the weight reduction seen with tirzepatide in participants with obesity or overweight with or without T2D.

Chronic nausea and vomiting are symptoms of a wide range of gastrointestinal and non-gastrointestinal conditions. Diagnosis can be challenging and requires a systematic and well-structured approach. If the initial investigation for structural, toxic and metabolic disorders is negative, digestive motility and gut-brain interaction disorders should be assessed. United European Gastroenterology (UEG) and the European Society for Neurogastroenterology and Motility (ESNM) identified the need for an updated, evidence-based clinical guideline for the management of chronic nausea and vomiting.

A multidisciplinary team of experts in the field, including European specialists and national societies, participated in the development of the guideline. Relevant questions were addressed through a literature review and statements were developed and voted on according to a Delphi process.

Ninety-eight statements were identified and voted following the Delphi process. Overall agreement was high, although the grade of scientific evidence was low in many areas. Disagreement was more evident for some pharmacological treatment options. A diagnostic algorithm was developed, focussing on the differentiating features between gastrointestinal motility and gut-brain interaction disorders with predominant nausea and vomiting.

These guidelines provide an evidence-based framework for the evaluation and treatment of patients with chronic nausea and vomiting.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have emerged as a leading pharmacologic for managing weight gain across most populations, including peri and postmenopausal women who frequently suffer from weight gain. There is a paucity of data about this specific population and how they respond to these medications. This review aims to discuss the data available about the use and effects of GLP-1 RAs in the peri and postmenopausal populations.

GLP-1 RAs are consistently the most effective pharmacologic for weight loss and can be a valuable tool for use in peri and postmenopausal women.

Additional research is needed to determine the risks and benefits and ideal use of GLP-1 RAs in peri and postmenopausal women.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for glycemic control and weight loss management in type 2 diabetes. Their use, however, is associated with a wide range of gastrointestinal adverse effects like nausea, vomiting, and abdominal discomfort. This case report presents a 59-year-old woman with a previous Roux-en-Y gastric bypass who was prescribed semaglutide, and subsequently developed intussusception with small bowel obstruction and chemical pancreatitis. The patient presented to the emergency department with nausea, vomiting, and epigastric pain. The patient's laboratory and radiographic studies revealed a long segment of small bowel intussusception, resulting in a small bowel obstruction and likely chemical pancreatitis. Laparoscopic surgical intervention was required, ultimately converted to a laparotomy for successful reduction of the intussusception. This case report underscores a potential complication that may be seen in patients prescribed GLP-1RAs with prior gastric Roux-en-Y surgeries. The adverse effect is likely attributable to altered gastrointestinal motility and delayed gastric emptying, mechanisms that may be exacerbated by the combination of bariatric-induced anatomical changes and the pharmacological actions of GLP-1RAs. Given the increasing prevalence of GLP-1RA use, emergency medicine clinicians must remain vigilant for these potential serious adverse effects, particularly in patients with complex gastrointestinal histories to ensure timely diagnosis and intervention.

Obesity is a complex and growing global concern, affecting one in eight individuals and compromising health, quality of life and life expectancy. It carries significant metabolic, cardiovascular, oncological, hepatorenal, skeletal and psychiatric risks, imposing substantial costs on health-care systems. Traditional treatments have often been ineffective or have led to relapse after lifestyle changes. Whereas bariatric surgery is effective, it also involves risks such as mortality and hospitalisation. Semaglutide, licensed in 2018, is a synthetic analogue of glucagon-like peptide 1 which regulates glucose metabolism and gastrointestinal (GI) motility. Studies show that semaglutide, administered either weekly and subcutaneously, or daily orally, induces an average weight loss of -11.62 kg compared to placebo and reduces waist circumference by up to -9.4 cm. It also improves blood pressure, fasting glucose levels, C-reactive protein levels and lipid profiles. The most common adverse events are mild-to-moderate GI complaints occurring more frequently with daily administration than weekly doses; hypoglycaemia is more common without lifestyle intervention. Weight regain often follows semaglutide withdrawal. Furthermore, semaglutide offers cardiovascular benefits for patients with established atherosclerotic cardiovascular disease (CVD), lowers the risk of kidney outcomes and cardiovascular-related death, resolves nonalcoholic steatohepatitis in many cases, and positively impacts mental health and quality of life. In conclusion, semaglutide therapy could significantly benefit many adults regarding CVD and mortality if made widely accessible. Ethical and financial considerations must be addressed for personalised obesity treatment approaches.

To assess glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) and sodium-glucose cotransporter protein-2 inhibitors (SGLT-2 inhibitors) in patients with metabolic dysfunction-associated steatotic liver disease or metabolic dysfunction-associated steatohepatitis (previously known as nonalcoholic fatty liver disease [NAFLD] and nonalcoholic steatohepatitis [NASH]), we performed a systematic review and network meta-analysis of randomized controlled trials.

The study searched Pubmed, Embase, the Cochrane Library, and Web of Science databases up to November 26, 2023. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias.

Thirty-seven studies were included in the analysis. GLP-1 receptor agonists were found to be more effective than placebo in resolving NASH (relative risk: 2.48, 95% CI:1.86 to 3.30). Both drugs were superior to placebo in reducing liver fat content, as well as decreasing levels of liver enzyme. Network meta-analysis indicated that SGLT-2 inhibitors were more effective than GLP-1 receptor agonists in reducing alanine aminotransferase and aspartate aminotransferase levels. According to the surface under the cumulative probability ranking curve values, GLP-1 receptor agonists and SGLT-2 inhibitors consistently ranked among the top 2 in terms of reducing anthropometric data compared to other included drugs.

GLP-1 receptor agonists and SGLT-2 inhibitors have significant effects on reducing liver fat content and liver enzymes in NAFLD or NASH patients compared to placebo. GLP-1 receptor agonists were found to be superior to placebo in resolving NASH. SGLT-2 inhibitors were more effective than GLP-1 receptor agonists in reducing alanine aminotransferase and aspartate aminotransferase levels.

Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a recognized complication of long-standing diabetes. Its pathophysiology involves, amongst other mechanisms, autonomic dysfunction due to vagal nerve damage, impaired smooth muscle contractility, and hormonal dysregulation of intestinal motility. During Ramadan, fasting causes significant dietary changes due to prolonged fasting and the consumption of large meals for Iftar (breaking of fast), which may unmask or worsen gastroparesis symptoms in individuals with diabetes. Symptoms such as early satiety, bloating, nausea, and glycemic fluctuations can further complicate diabetes management during fasting. This paper highlights the relationship between Ramadan fasting and gastroparesis in individuals with diabetes, exploring underlying mechanisms, clinical manifestations, diagnostic approaches, and management strategies. A multidisciplinary approach involving dietary modifications, medication adjustments, lifestyle changes, and individualized medical counseling is essential for safe fasting, alongside the option to avoid fasting in individuals who are deemed too high at risk for fasting. Further research is needed to assess the prevalence of subclinical gastroparesis in fasting individuals with diabetes and to optimize risk stratification and management in these patients.

Glucagon-like peptide-1 receptor (GLP-1R) agonists have been increasingly prescribed for weight loss and glycemic control. The potential side effect of slowed gastric emptying may increase risk of regurgitation and aspiration. Our primary aim was to investigate the incidence of retained gastric contents (RGCs) among appropriately fasted patients taking a GLP-1R agonist compared to those not taking a GLP-1R agonist presenting for upper gastrointestinal endoscopy (UE).

A retrospective chart review of patients undergoing UE was conducted. For the GLP-1R group, included were patients aged 18 years or older who had documentation of taking a GLP-1R agonist within 30 days prior to the procedure, adhered to standard fasting guidelines, and had clear documentation in the electronic medical record of gastric findings during endoscopy. This group was compared to a group of agematched controls. The primary outcome was the incidence of RGCs. Secondary outcome included a propensity-weighted analysis of the odds ratio of taking a GLP-1R and having RGCs.

Included were 940 patients who presented for UE between July 2022 and December 2023 (470 GLP-1R and 470 controls). RGCs were found in 59/470 (12.6 %) of GLP-1R patients compared to 26/470 (5.5 %) of controls (P < 0.001). Propensity-weighted analysis found a significant association between the use of GLP-1R and retained gastric contents [OR = 1.92, 95 % CI (1.04, 3.53)].

A higher incidence of RGCs was found in appropriately fasted patients on a GLP-1R agonist who presented for UE. After controlling for the differences between the two study groups, RGC's were correlated to GLP-1R agonist use. Anesthesiologists should remain vigilant regarding a potential increased risk of RGCs in appropriately fasted patients taking a GLP-1R agonist who present for surgery.

The GLP-1 receptor-based agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) are major twenty first century breakthroughs in diabetes and obesity medicine but there are important safety considerations regarding the perioperative and periprocedural management of individuals who are treated with these agents. GLP-1RAs have been linked to an increased risk of retained gastric contents and pulmonary aspiration while SGLT2i can be associated with diabetic ketoacidosis. This manuscript provides a narrative review of the available evidence for perioperative and periprocedural risks in people prescribed GLP-1RAs and SGLT2i. The authors provide expert opinion-driven recommendations and algorithms on how to safely manage GLP-1RAs and SGLT2i under perioperative/periprocedural settings.

In patients with inflammatory bowel disease (IBD), multimorbidity with obesity and type 2 diabetes is common and increasing. Glucagon-like peptide 1 (GLP-1) receptor agonists are increasingly being prescribed for patients with IBD, yet their impact on patients with IBD is largely unknown. We aimed to assess the impact of GLP-1 receptor agonists on the course of IBD.

We identified all IBD patients prescribed GLP-1 receptor agonists at a large academic healthcare network between 2009 and 2023. We analyzed demographics and IBD characteristics in the year pre- and post-GLP-1 receptor agonist prescription and matched them to non-IBD controls. Our primary outcome was IBD exacerbation in the year following GLP-1 receptor agonist initiation, measured as a composite of IBD-related hospitalization, corticosteroid prescription, medication escalation or changes, or IBD-related surgery. Secondary outcomes included change in metabolic risk factors.

Overall, 224 patients met inclusion criteria. At GLP-1 receptor agonist initiation, the median age was 54 years, 63% were female, 77% were White, and median BMI was 33.2 kg/m2. Compared to the 12-month period prior to GLP-1 receptor agonist initiation, in the 12 months post-GLP-1 receptor agonist initiation, there was no change in rates of IBD exacerbation, IBD-related hospitalization, steroids prescription, medication escalation or changes, or IBD-related surgery. There was a significant decrease in BMI in the year following GLP-1 receptor agonist initiation (median BMI 33.5 vs 31.6 kg/m2, P < .01), with rates of decrease comparable to non-IBD matched controls.

In patients with IBD, GLP-1 receptor agonists are effective for weight loss and associated with few episodes of disease exacerbation.

The evident influence of GLP-1 agonists as semaglutide on gastric emptying even in adherence to recommended fasting protocols instigates debates.

To investigate the effect of semaglutide on gastric content by gastric ultrasonography in volunteers.

Private hospital.

The present study is an observational, cross-sectional, and single-center study. We included 30 consecutive volunteers aged ≥18 years who had undergone a minimum fasting period of 8 hours for solid foods and 2 hours for clear, residue-free liquids. The intervention group consisted of 15 volunteers who had used semaglutide within the last 7 days, whereas the control group consisted of 15 volunteers who had never used semaglutide. The main objective was to determine whether the stomach was full or not.

Between June 2023 and August 2023, a total of 30 adult volunteers were included in the study, and no participant was excluded. The semaglutide group exhibited a higher prevalence of full stomach (11 of 15 [73%] versus 1 of 15 [7%], P < .001; adjusted to age P = .003). The semaglutide group also exhibited a higher prevalence of early satiety (10 of 15 [67%] versus 0 of 15 [0%], P < .001), loss of appetite (10 of 15 [67%] versus 0 of 15 [0%], P < .001), gastric fullness (8 of 15 [53%] versus 0 of 15 [0%], P = .002), and nausea (7 of 15 [47%] versus 1 of 15 [7%], P = .035). Additionally, there is no case in the semaglutide group with no gastric contents.

The use of semaglutide is associated with full stomach even after appropriate overnight fasting. Semaglutide is also associated with increased gastrointestinal symptoms such as loss of appetite, early satiety, gastric fullness, and nausea.

To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity.

We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation.

Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of -4.57 kg (95% CI -5.35 to -3.78), mean BMI reduction of -2.07 kg/m2 (95% CI -2.53 to -1.62), and mean waist circumference reduction of -4.55 cm (95% CI -5.72 to -3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations.

GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.

This study aimed to determine the effects of polyethylene glycol loxenatide (PEG-Loxe), a glucagon-like peptide-1 receptor agonist, on a three-point major adverse cardiovascular event (3P-MACE) in patients with type 2 diabetes mellitus (T2DM). The study was conducted in six tertiary hospitals in three cities in China. Large language models were used to retrospectively screen and include 12,341 patients with T2DM who had either cardiovascular disease or cardiovascular risk factors. The patients were divided into the PEG-Loxe cohort (treated with PEG-Loxe, n = 1282) and the control cohort (treated with incretin glucose-lowering agents, n = 11,059). After a median follow-up of 4.0 years, 3P-MACE occurred in 51 (4.0%) and 1263 (11.4%) patients in PEG-Loxe and control cohorts, respectively (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.94; p = 0.019). In the PEG-Loxe versus control cohorts, 21 (1.6%) versus 476 (4.3%) patients experienced nonfatal stroke (HR 0.63; p = 0.041), whereas 22 (1.7%) versus 545 (4.9%) experienced nonfatal myocardial infarction (HR 0.66; p = 0.058), and the incidence of cardiovascular death was 8 (0.6%) versus 240 (2.2%), respectively (HR 0.56; p = 0.118). We found a significantly lower incidence of first nonfatal myocardial infarction, nonfatal stroke, or cardiovascular deaths in the PEG-Loxe cohort than the control cohort.

Peptides are able to bind to difficult disease targets with high potency and specificity, providing great opportunities to meet unmet medical requirements. Nevertheless, the unique features of peptides, such as their small size, high structural flexibility, and scarce data availability, bring extra challenges to the design process. Firstly, this review sums up the application of peptide drugs in treating diseases. Then, the review probes into the advantages of Deep Neural Networks (DNNs) in predicting and designing peptide structures. DNNs have demonstrated remarkable capabilities in structural prediction, enabling accurate three-dimensional modeling of peptide drugs through models like AlphaFold and its successors. Finally, the review deliberates on the challenges and coping strategies of DNNs in the development of peptide drugs, along with future research directions. Future research directions focus on further improving the accuracy and efficiency of DNN-based peptide drug design, exploring novel applications of peptide drugs, and accelerating their clinical translation. With continuous advancements in technology and data accumulation, DNNs are poised to play an increasingly crucial role in the field of peptide drug development.

Video capsule endoscopy (VCE) is valuable for assessing conditions like GI bleeding, anemia, and inflammatory bowel disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for diabetes and weight loss, with their pharmacologic effects including delayed gastric emptying. This study investigates the impact of GLP-1RA use on VCE outcomes in patients with diabetes.

This retrospective cohort study involves patients with diabetes undergoing VCE while on GLP-1RAs matched in a 1:1 ratio with control subjects, who are not on GLP-1RAs, based on demographics and diabetes-related factors. The primary outcome was gastric transit time in VCE studies, whereas secondary outcomes were incomplete small-bowel evaluation and small-bowel transit time.

In the GLP-1RA cohort with 68 patients, 5 (7%) experienced failure to pass the video capsule through the stomach; all control subjects passed the video capsule successfully (P = .06). GLP-1RA patients had a longer gastric transit time (99.3 ± 134.2 minutes) compared with control subjects (25.3 ± 31.6 minutes, P < .001). Multivariate analysis revealed GLP-1RA use was associated with an increased gastric transit time by 74.5 minutes (95% confidence interval, 33.8-115.2; P < .001) compared with control subjects, after adjusting for relevant factors. Sixteen GLP-1RA patients (23.5%) experienced incomplete passage of the video capsule through the small intestine, a significantly higher rate compared with 3 patients in the control group (4.4%, P < .01).

GLP-1RA use is associated with a prolonged gastric transit time and a higher rate of incomplete small-bowel evaluation during VCE. Future studies may be crucial for evaluating strategies to mitigate these effects.

With the growing use of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists as anti-obesity medication it is becoming increasingly important to examine its consequences in the peri-operative period. GLP-1R agonists are known for their effects of glucose-lowering and gastroparesis the latter causing some safety concerns regarding induction of anaesthesia, more specifically the risk of pulmonary aspiration. This article gathers the available evidence on this subject in addition to the already established guidelines. Current evidence makes us assume there is indeed an increased level of gastroparesis, but there are no studies to date with evidential confirmation of a presumed elevated risk of pulmonary aspiration. Future perspectives should focus on the actual risk of pulmonary aspiration and the possible implementation of ultrasound in the preoperative assessment.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to cause delayed gastric emptying; however, the effect on clinical outcomes during upper endoscopy and colonoscopy remains unclear. We conducted a meta-analysis to reconcile the data.

Online databases were searched for studies evaluating GLP-1RAs versus a control group (no GLP-1RAs) in patients undergoing endoscopy. The outcomes of interest were rate of retained gastric contents (RGCs), aborted procedures, aspiration events, and subjective bowel preparation quality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model.

Twenty-three studies with 77,152 patients (4449 in the GLP-1RA arm and 72,703 in the control arm) were included. Mean patient age ranged from 47.6 to 72 years, and 58.4% were women. As compared with the control group, the GLP-1RA group had higher odds of RGCs (OR, 15.39; 95% CI, 4.65-50.99; P < .01) and aborted procedures (OR, 13.86; 95% CI, 4.42-43.43; P < .01). No significant differences were observed between the 2 groups in terms of aspiration events (OR, 21.06; 95% CI, .13-3379.01; P = .24) and subjective bowel preparation quality (OR, .94; 95% CI, .67-1.31; P = .83).

Although statistical significance was reached in terms of visible RGCs and early termination of endoscopies in patients on GLP-1RAs, these events were overall rare. GLP-1RAs do not appear to pose significant risk, as the odds of developing aspiration were comparable in the 2 groups.

Diabetes mellitus (DM) is a persistent and steadily progressing metabolic condition distinguished by unregulated high levels of blood glucose. GLP1 receptor agonists have recently gained recognition as first-line therapies in selected instances, as per the updated ADA guidelines, highlighting their efficacy not only in glycemic control but also in their broader health benefits. Nonetheless, the efficacy of GLP-1 is limited by its brief duration of action, rapid clearance from the body, and challenges associated with subcutaneous administration. In this study, we examined the potential diabetes-mitigating effects of a genetically engineered strain of Escherichia coli Nissle 1917 (EcN)-GLP-1, previously developed by our group. We utilized mouse models for both Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) to assess its efficacy. In the case of T1DM mice, the results revealed that EcN-GLP-1 resulted in a notable decrease in blood glucose levels. Furthermore, it exhibited a protective influence on the structural integrity of islet β-cells; downregulated the expressions of key inflammatory markers such as TLR-4, p-NF-κB/NF-κB, and Bax/Bcl-2; promoted the insulin secretion; and reinstated the perturbed diversity of microbial species to a normal state. Similarly, EcN-GLP-1 had a pronounced impact on T2DM mice, manifesting increased presence of islet β-cells, decreased inflammatory response and apoptosis, and regulation of lipid metabolism in the liver. In summary, the genetically modified EcN-GLP-1 strain demonstrates the ability to alleviate diabetes by enhancing the islet β-cell population, mitigating inflammatory reactions and apoptosis, optimizing liver lipid metabolism, and reinstating a balanced microbial diversity. These findings hold promise as a potential avenue for treating DM.

Peptides are attracting a growing interest for therapeutic applications in biomedicine. In Parkinson's disease (PD), different human endogenous peptides have been associated with beneficial effects, including protein aggregation inhibition, reduced inflammation, or the protection of dopaminergic neurons. Such effects seem to be connected to the spatial arrangement of peptide side chains, and many of these human molecules share common conformational traits, displaying a distinctive amphipathic and cationic helical structure, which is believed to be crucial for their activities. This review delves into the relationship between these structural properties and the current evidence connecting biogenic peptides to the amelioration of PD symptoms. We discuss their implications in the disease, the different mechanisms of action, their state of validation, and their therapeutic potential.

Obesity, a pervasive global health challenge affecting more than 2 billion people, requires comprehensive interventions. Traditional approaches, including lifestyle modification, and diverse drugs targeting a gastrointestinal hormone, including glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (Liraglutide, Semaglutide, Exenatide, Albiglutide, Dulaglutide, Lixisenatide, Orlistat, Phentermine/Topiramate, Lorcaserin, Sibutramine, and Rimonabant) offer tailored strategies; yet their effectiveness is limited and some drugs were taken off the market. Moreover, various surgical modalities, such as Roux-en-Y Bypass surgery, sleeve gastrectomy, intragastric balloons, biliopancreatic diversion with duodenal switch, laparoscopic adjustable gastric band, and vagal nerve blockade can be considered but are associated with numerous side effects and require careful monitoring. Consequently, there is a pressing need for novel anti-obesity treatments.

This comprehensive review was based on the available data to discuss the traditional pharmaceutical and surgical therapeutical strategies for obesity, going further to discuss tirzepatide's mode of action, its outcomes for obesity, and the associated side effects.

In this landscape, tirzepatide, initially designed for type 2 diabetes management, emerges as a potential game-changer. Functioning as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, it not only addresses control but also introduces a fresh perspective on weight reduction. This review intricately explores tirzepatide's mechanism, dissecting insights from clinical studies and positioning it as a major force in obesity treatment.

In the middle of significant shifts in obesity management, tirzepatide presents itself as a promising and cost-effective intervention. Its Food and Drug Administration approval marks a milestone in the realm of obesity therapeutics. Going beyond a recapitulation of findings, the conclusion emphasizes the imperative for ongoing exploration and vigilant safety monitoring in tirzepatide's application.

GLP-1 receptor agonist (GLP-1RA) have been developed to address the global burden of obesity and are renowned for their safety and efficacy. These medications influence hunger and satiety, reducing energy intake and promoting weight loss. Despite their benefits, GLP-1RAmay cause a slowed gastric emptying, leading to gastrointestinal symptoms. This study examines how food properties and meal composition affect these symptoms. Dietary recommendations are provided, particularly for evening meals, focusing on how different foods and nutrients can influence the rate of gastric emptying, to improve patient compliance and prevent interruption in weight loss.

GlP-1 receptor agonists are a class of medications that are becoming increasingly popular. Large trials have shown that their use provides reliable weight loss in obese patients and improved glycemic control in diabetic patients. Its use also has broader implications for overall metabolic health and has been shown to improve cardiovascular outcomes in high-risk populations. Glucagon-like peptide 1 receptors cause multiple effects in the body through stimulation of receptors expressed in a broad range of tissues including the pancreas, liver, gastrointestinal tract, kidneys, heart, endothelium, muscle, and brain. For the anesthesia professionals the effects of these medications on gastric emptying is important.

Recent evidence suggests that perioperative semaglutide use is associated with increased residual gastric content (RGC) and risk of bronchoaspiration under anesthesia. We compared the occurrence of increased RGC in semaglutide users and non-users undergoing esophagogastroduodenoscopy to define the time interval at which RGC becomes comparable between groups.

This was a single-center retrospective electronic chart review at a tertiary hospital. Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-July/2023 were included and divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy. Univariate and multivariate logistic regression were performed to explore which factors were associated with increased RGC, defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content.

Among the 1094 (SG = 123; NSG = 971) patients included, increased RGC was observed in 56 (5.12%), being 25 (20.33%) in the SG and 31 (3.19%) in the NSG (p < 0.001). Following weighted analysis, the presence of ongoing digestive symptoms (nausea/vomiting, dyspepsia, and/or bloating/abdominal distension) pre-esophagogastroduodenoscopy [OR = 15.1 (95% confidence interval (CI) 9.85-23.45)] and the time intervals of preoperative semaglutide interruption < 8 days [OR 10.0 (95%CI 6.67-15.65)] and 8-14 days [4.59 (95%CI 2.91-7.37)] remained significantly associated with increased RGC. Following inverse probability treatment weighting adjustment including a composite variable 'time intervals of semaglutide interruption' versus 'presence of ongoing digestive symptoms', only time intervals > 14 days and without digestive symptoms showed no association with increased RGC [OR = 0.77 (95%CI 0.22-2.01)].

Perioperative semaglutide use is associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Preoperative discontinuation of > 21 days and > 14 days in patients with and without ongoing digestive symptoms, respectively, resulted in RGC similar to non-semaglutide users.

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight loss and glycemic control. In addition, the present investigation explores recent clinical studies demonstrating the effectiveness of GLP-1 RAs in diabetic and nondiabetic populations, highlighting their potential in addressing obesity even in those without T2DM and describing probable benefits to cardiovascular health. Finally, our investigation outlines the importance of future research to further define the potential benefits of GLP-1 RAs.

Adzuki bean (AB) is a legume with a low glycemic index and is traditionally used in Asian cultures to modulate type 2 diabetes (T2D). Our objectives were to characterize the functional peptides from purified AB β-vignin after simulated gastrointestinal digestion in comparison to soybean β-conglycinin, to evaluate their DPP IV inhibitory capacity, and to determine in vitro the effect of digested AB β-vignin on diabetic-related outcomes using HepG2 cells in healthy and insulin-resistant states. Five peptides (215-742 Da) from AB β-vignin and five peptides (215-447 Da) from β-conglycinin were identified to exhibit bioactivity as DPP IV inhibitors. Molecular docking demonstrated peptides could bind to DPP IV at the same binding site as a diabetic medication, linagliptin. Digested AB β-vignin significantly increased (p < 0.05) hepatic glucose uptake (> 290 %) via DPP IV inhibition (> 40 %) in healthy and insulin-resistant states. IRS-1, Akt-1, and Glut 2 increased after treating cells with digested AB β-vignin in healthy and insulin-resistant states.

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats.

Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated.

SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group.

These results indicate SEMA's neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.