Introduction:
Glucagon-like peptide-1 receptor agonist (GLP-1RAs) and more recently Twin-Cretins (GLP+GIP) are frequently used for patients with diabetes and associated obesity. In part their use is increasing based on the recommendation by the ADA and the EASD due to associated comorbidities. Their mechanism of action includes delayed gastric emptying; however, the relation between these drugs and new onset gastroparesis (GP) has not been evaluated. We assessed the risk of new-onset GP in patients with Type 2 diabetes (T2D) treated with GLP-1RAs.

Methods:
We utilized the TriNetX multi-institutional database (~88 million patients) to examine the risk of new diagnosis of GP (ICD-10 code K31.84) in adult patients (age >18) with T2D who were prescribed GLP-1RAs (dulaglutide, semaglutide, liraglutide, lixisenatide, exenatide, tirzepatide, or albiglutide) between January 2021 and December 2022. We compared this group with patients who had T2D but were never prescribed GLP-1RAs. Patients with a history of bariatric surgery, fundoplication, celiac disease, IBD, or GI cancers were excluded from the study. In addition, patients with history of GP prior to GLP-1RA prescription were excluded. To ensure balanced cohorts, we performed 1:1 propensity score matching for demographics, diabetes, neurological disorders, medications, HbA1c, BMI, and multiple comorbidities (Table 1).

Results:
In our study cohort, there were 2,203,082 and 336,655 patients with T2D who received no GLP-1RAs or received GLP-1RA respectively. After propensity score matching, there were 336,655 in each cohort. Patients were predominantly female and white (Table 1), however we had nearly 30% of the cohort representing minorities. As expected patients with T2D who were prescribed GLP analogs had higher BMI and poor glucose control (Table 1). Patients with T2D prescribed GLP-1 RAs had an increased risk of GP at 6, 9, 12, 18 and at 24 months (Table 2). The odds ratio for GP significantly increased after 6 months through 24 months after controlling for different risk factors.

Conclusion:
We conclude an association between GLP-1RA prescription and increased GP risk in patients with T2D in this large study. We propose ongoing long-term clinical monitoring and further research in patients with T2D who are prescribed GLP analogs.

Samita Garg

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