Diabetes/Prediabetes/Hypoglycemia
William E. Jenkins, MD
Internal Medicine Resident
University at Buffalo
Buffalo, New York, United States
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are used in managing type 2 diabetes mellitus (T2DM) and weight loss. However, their use is associated with various gastrointestinal adverse effects, notably gastroparesis, attributed to their role in delaying gastric emptying and enhancing satiety. Case studies and recent retrospective analyses in non-diabetic, obese populations have indicated a heightened incidence of gastroparesis linked to GLP-1 RA usage. Despite these findings, there is a notable gap in the literature regarding the incidence of gastroparesis among patients with T2DM treated with GLP-1 RA, especially when compared to other treatment modalities such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which are not traditionally associated with an increased risk of gastroparesis. This study seeks to ascertain whether semaglutide, a GLP-1 RA, is associated with a significant rise in gastroparesis incidence compared to sitagliptin, a DPP-4 inhibitor, in patients with pre-existing T2DM, focusing on the initial six months following treatment commencement.
Methods: In this retrospective cohort study, we utilized data sourced from the TriNetX electronic health records global collaborative network, which included 131,466,594 patients. The target population of this investigation was patients with T2DM who had no prior ICD-10 code for gastroparesis or usage of GLP-1 RA or DPP-4 inhibitors in the five years preceding their initial semaglutide treatment. A comparative group meeting the same inclusion criteria was identified among patients who commenced treatment with sitagliptin. Before matching, the patient population consisted of 54,951 in the semaglutide cohort and 118,123 in the sitagliptin cohort. To mitigate potential confounding factors such as age, sex, alcohol consumption, smoking habits, and obesity, a propensity score match was executed, resulting in two well-balanced cohorts (n=53,989 each).
Results: Within the 6 months following initiation of semaglutide or sitagliptin, the incidence of gastroparesis was slightly higher in the semaglutide group (154 events) compared to the sitagliptin group (137 events), but this difference was not statistically significant (p = 0.3183). The relative risk associated with semaglutide was 1.124 (95% CI: 0.893-1.415), indicating no significant increase in risk compared to sitagliptin. Similarly, no significant differences were observed within 1 year of starting semaglutide as compared to sitaglitptin.
Discussion/Conclusion: Our data show that semaglutide is not associated with a significant increase in gastroparesis within six months of initiation compared to sitagliptin in patients with T2DM and that overall incidence is low. Prospective studies are required to elucidate if there is an increased risk of gastroparesis with GLP-1 RA as compared to other hypoglycemic therapies, given that this patient population is already at a higher baseline risk.