1181

EXPLORING GASTROINTESTINAL AND HEPATOBILIARY ADVERSE EVENTS IN GLP-1 RECEPTOR AGONISTS THERAPY: A LARGE COHORT RETROSPECTIVE STUDY

Date
May 21, 2024
Explore related products in the following collection:

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are integral in managing type 2 diabetes. However, their long-term impact on gastrointestinal and hepatobiliary health remains uncertain. Addressing the gap in existing literature, our retrospective study, using a large cohort from the TriNetX database with a 5-year follow-up, investigates these potential adverse events, including the often-debated risk of GI cancers.

Methods: This retrospective study utilized data from the TriNetX database, analyzing a large cohort over five years. Propensity score matching (PSM) was employed to create six cohorts, each comparing oral semaglutide, injectable formulations of semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide against control group. We assessed the incidence of cholecystitis, choledocholithiasis, cholangitis, pancreatitis, gastroparesis, biliary and pancreatic cancer, and gastroesophageal reflux disease (GERD), using hazard ratios (HRs) and P values for statistical significance.

Results: Our analysis elucidated various risk profiles across the GLP-1 RA spectrum. The patient data included equal numbers in the treatment and control groups for each medication: oral semaglutide (35,744 patients in each group), injectable semaglutide (173,437 patients in each group),(Table 1,2) liraglutide (130,637 patients in each group), dulaglutide (297,047 patients in each group), exenatide (36,019 patients in each group), and lixisenatide (9,360 patients in each group).Oral semaglutide exhibited a non-significant difference in cholecystitis (HR: 0.846, P=0.070) and gastroparesis risks compared to control group (HR: 0.840, P=0.056). Injectable semaglutide was linked with increased gastroparesis (HR: 1.203, P<0.001) and pancreatitis risks (HR: 1.129, P<0.001). Liraglutide injections showed increased occurrences of cholangitis (HR: 1.218, P=0.004), pancreatitis (HR: 1.312, P<0.001), and gastroparesis (HR: 1.433, P<0.001). Dulaglutide was associated with higher pancreatitis risk (HR: 1.097, P<0.001). Exenatide increased risks of gastroparesis (HR: 1.394, P<0.001), cholangitis (HR: 1.421, P=0.003), and pancreatitis (HR: 1.250, P<0.001). Lixisenatide presented an elevated gastroparesis risk (HR: 1.437, P=0.004). Notably, no GLP-1 RA formulation was found to significantly increase the risk of biliary or pancreatic cancers.

Conclusion: This large retrospective study provides valuable insights into the safety profile of GLP-1 RAs, particularly concerning gastrointestinal and hepatobiliary side effects. Our findings indicate that GLP-1 RAs do not show an increase in GI cancer risk which is a significant clinical takeaway. However, caution and vigilance remain key, especially considering that each GLP-1 RA formulation carries its own spectrum of gastrointestinal and hepatobiliary side effects.

Tracks

Related Products

Thumbnail for MSC-EV PROTECTS AGAINST IMMUNOLOGICAL LIVER INJURY BY SUPPRESSING FERROPTOSIS VIA ACTIVATION OF THE NRF2/GPX4 SIGNAL AXIS
MSC-EV PROTECTS AGAINST IMMUNOLOGICAL LIVER INJURY BY SUPPRESSING FERROPTOSIS VIA ACTIVATION OF THE NRF2/GPX4 SIGNAL AXIS
Ferroptosis plays an important role in the pathogenesis of various liver diseases, yet it has rarely been investigated in human autoimmune hepatitis (AIH)…
Thumbnail for AASLD Presidential Plenary
AASLD Presidential Plenary
ASSOCIATION OF GLUCAGON-LIKE PEPTIDE-1 AGONISTS WITH CIRRHOSIS AND HEPATOCELLULAR CANCER IN METABOLIC DYSFUNCTION ASSOCIATED STEATOTIC LIVER DISEASE (MASLD)
Thumbnail for FEMALES WITH AUTOIMMUNE LIVER DISEASES ARE AT INCREASED RISK OF MAJOR ADVERSE CARDIOVASCULAR OUTCOMES: A NATIONWIDE MATCHED COHORT STUDY
FEMALES WITH AUTOIMMUNE LIVER DISEASES ARE AT INCREASED RISK OF MAJOR ADVERSE CARDIOVASCULAR OUTCOMES: A NATIONWIDE MATCHED COHORT STUDY
Cardiovascular disease (CVD) remains a leading cause of death in women. The Atherosclerotic Cardiovascular Disease 10-year risk score recommended by the American College of Cardiology does not encompass chronic inflammatory diseases, which is associated with increased CVD risk…
Thumbnail for AIH-MASLD OVERLAP IS PREVALENT IN A NORTH AMERICAN AIH COHORT BUT HAS SIMILAR CLINICAL FEATURES AND OUTCOMES AS AIH ALONE
AIH-MASLD OVERLAP IS PREVALENT IN A NORTH AMERICAN AIH COHORT BUT HAS SIMILAR CLINICAL FEATURES AND OUTCOMES AS AIH ALONE
INTRODUCTION: Coexistence of metabolic dysfunction-associated liver disease (MASLD) and autoimmune hepatitis (AIH) could lead to more severe disease with poorer outcomes…