Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed for the management of type 2 diabetes mellitus (T2DM). However, the potential connection between GLP-1 RAs and the risk of pancreatitis presents a complex and nuanced issue. Although these drugs are effective in improving blood sugar control and cardiovascular health, their association with pancreatitis remains an area of concern. Our study aims to evaluate the association between the use of GLP-1 RAs, considered as a single class, and the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus (T2DM) in the United States. Methods: Data were retrieved from the TriNetX research database using the US Collaborative Network, which included information from 61 healthcare organizations within the U.S. Patients diagnosed with T2DM were categorized into two cohorts: one consisting of the patients prescribed with GLP-1 RAs and the other comprising patients who did not receive GLP-1 RAs. Of this class of medications, the agents analyzed were dulaglutide, lixisenatide, exenatide, liraglutide, and semaglutide. Using a 1:1 propensity score matching (PSM) model, we matched patients of both cohorts based on baseline demographics, comorbidities (hypertensive disorders, ischemic heart disease, gallstones, annular pancreas, alcohol use disorders, hypertriglyceridemia, hypercalcemia, cystic fibrosis, and cannabis use), medications known to cause drug-related pancreatitis, and laboratory values. Results: Of 969,240 patients with T2DM, 9.7% (93,608) were on GLP-1 RA, and 90.3% (875,632) were not. After PSM, the sample included 81,872 patients in each cohort. The risk of pancreatitis between the two groups was not statistically different between the two cohorts at 6 months at (0.1% vs. 0.1%, p = 0.04), and remained without significant increase with time; at 1 year (0.1% vs. 0.2%, p = 0.02), 3 years (0.2% vs. 0.3%, p = 0.001), and 5 years (0.3% vs. 0.4%, p < 0.001). The lifetime risk of developing pancreatitis in patients on GLP-1 RA was lower (0.3% vs. 0.4%, p < 0.001). Conclusions: In our comorbidity-free U.S.-based population with T2DM, the use of GLP-1 RAs did not increase their risk of pancreatitis. Their use was associated with a lower lifetime risk of pancreatitis.

Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX’s deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Results: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. Conclusion: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. Methods: We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m², and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients’ baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. Results: A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. Conclusion: The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.

Background/Objectives: Glucagon-like peptide-1 receptor agonists are increasingly used worldwide for weight and hyperglycemia management. There is an ongoing debate on the presence of increased gastric residue, leading to complications such as aspiration and overall safety in patients receiving upper gastrointestinal endoscopy. We aimed to study the effect of GLP-RAs on endoscopy outcomes. Methods: We conducted a detailed search of online databases to select the studies which provided details of the effects of GLP-RAs on patients undergoing endoscopy. The outcomes of interest were odds of retained gastric content (RGC), aspiration risk, and aborted and repeated procedures. A random effect model was used to calculate the pooled odds of outcomes with a 95% CI. We further calculated the pooled odds of predictive factors associated with an increased rate of retained gastric residues in the study population. Results: We included 12 studies with a total of 105,515 patients, of which 32,144 were on GLP-1 RAs and 73,273 were in the control group. A total of 234 (0.73%) aspiration events in GLP-RA users were noted compared to 257 (0.35%) events in the control group. No increased odds (1.26, 95% CI 0.86–1.87, I² 34%) of aspiration were found in GLP-1 users compared to the non-GLP-1 group. Patients on GLP-1 RA had increased RGC compared to the control group (OR 6.30, 95% CI 5.30–7.49, I² 0%). The pooled odds of aborted (OR 5.50, 95% CI 3.25–9.32, I² 0%) and repeated procedures (OR 2.19, 95% CI 1.42–3.38, I² 0%) were significantly higher in GLP-1 RA users. Patients taking Tirazepatide had the highest percentage of RGC (18.9%), while exenatide users had the lowest rate (6.2%) of food retention. Patients undergoing concomitant colonoscopy were found to have significantly low pooled odds of RGC (OR 0.26, 95% CI 0.04–0.48). GLP-1 RAs use was independently associated with increased odds of RGC (3.91, 95% CI 3.21–4.62, I² 0%). The results were homogenous and stayed consistent in the sensitivity analysis. Conclusions: Although the odds of RGC and aborted procedures are high in the GLP-1 RAs group compared to the control, no significant difference in the odds of aspiration was found between the two groups. Simple measures such as a clear liquid diet for 24 h, as routinely set for patients undergoing colonoscopy, may reduce the risk of retaining gastric residue in these patient populations.

Background: Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child‐Pugh class C cirrhosis (CPC).Methods: We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM).Results: Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3‐year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs.Conclusion: Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Background: SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2’s impact on decompensation in previously compensated cirrhotic patients. Methods: We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX’s deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. Results: Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. Conclusions: SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.