Cosmos Study

Delayed Gastric Emptying More Likely, Gallstones and Ileus Less Likely for Diabetic Patients on GLP-1 Medications Compared to Diabetics on Other Treatments

May 1, 2024

Team A:Kersten Bartelt, RNJoe Deckert, PhD

Team B:Steve Allen, MDBrendan Joyce

Key Findings

Diabetic patients prescribed four of the five glucagon-like peptide-1 receptor agonist (GLP-1) medications studied experienced increased likelihood of delayed gastric emptying (gastroparesis) compared to those not on a GLP-1 medication.
Diabetic patients prescribed GLP-1 medications are less likely to be diagnosed with gallstones or ileus compared to diabetic patients not on GLP-1 medications.

Gastrointestinal (GI) side effects including delayed gastric emptying, gallstones, and ileus have been associated with glucagon-like peptide-1 receptor agonist (GLP-1) medications.^1,2 The U.S. Food & Drug Administration (FDA) required a safety label for Ozempic (semaglutide) warning of the potential risk of ileus, a condition characterized by impaired intestinal motility.^3,4

To further understand the correlation between GLP-1 medications and GI side effects, we studied 12 million diabetic patients, including 4.6 million on GLP-1 medications and 7.4 million not on GLP-1 medications. We wanted to increase the likelihood that we were studying only patients who were being actively managed. For the patients on GLP-1 medications, that prescription served as adequate evidence. For patients not on GLP-1 medications, we included only those who had a completed HbA1c test. We adjusted for patient sex, age, social vulnerability, BMI classification, race, ethnicity, and insulin usage.

We found that delayed gastric emptying (gastroparesis) was more likely for diabetic patients on most GLP-1 medications studied compared to diabetics not on GLP-1 medications. Patients on exenatide had the greatest increase in likelihood of this condition (135%), while those on tirzepatide had a 29% reduction in likelihood. Gallstones and ileus were less likely for patients prescribed most of the GLP-1 medications studied compared to diabetic patients not prescribed a GLP-1 medication. Patients on semaglutide had a 22% reduced likelihood of gallstones while those on tirzepatide did not experience a statistically significant change in the likelihood. For ileus, tirzepatide had the greatest reduction in likelihood (62%) while exenatide had the lowest reduction (43%).

Figure 1

GI Side Effect Likelihood by GLP-1 Medication Among Diabetic Patients

Figure 1. The likelihood of diabetic patients being diagnosed with a GI side effect after a GLP-1 prescription.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 246 million patient records from 1,400 hospitals and more than 32,800 clinics from all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

References

He L, Wang J, Ping F, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: A systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2022;182(5):513. doi:10.1001/jamainternmed.2022.0338
Kalas MA, Galura GM, McCallum RW. Medication-Induced Gastroparesis: A Case Report. J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:23247096211051919. doi: 10.1177/23247096211051919. PMID: 34663102; PMCID: PMC8529310.
Drug safety-related labeling changes (SrLC). U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2183. Accessed January 17, 2024.
Durning V, Sachdev P. What is ileus? WebMD. Published December 4, 2023. https://www.webmd.com/digestive-disorders/what-is-ileus. Accessed January 17, 2024.