Glycemic therapies and the risk of gastrointestinal adverse events in veterans with type 2 diabetes

Aims To compare the risk of gastrointestinal adverse events in new users of glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and insulin glargine. Materials and Methods We conducted an active comparator, new user design study in veterans with type 2 diabetes who initiated one of these drug classes between 1 January 2018 and 31 December 2021 ( N = 141 080). Inverse probability weighted Cox regression models were used to relate drug class to outcomes of gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis and all‐cause death. Results There were 19 765 (14.0%) veterans initiated on GLP‐1RA, 75 058 (53.2%) on SGLT2i and 46 257 (32.8%) on insulin glargine. Compared to SGLT2i, GLP‐1RA had a higher hazard of gastroparesis (HR 1.65, 95% CI 1.33–2.05) but a similar mortality hazard. Compared to insulin glargine, GLP‐1RA had a higher hazard of gastroparesis (HR 1.24, 95% CI 1.02, 1.52), but a lower hazard of all‐cause death (HR 0.62, 95% CI 0.58, 0.66). Compared to SGLT2i, insulin glargine had a higher hazard of gastroparesis (HR 1.29, 95% CI 1.07, 1.56), intestinal obstruction (HR 1.26, 95% CI 1.11, 1.43) and all‐cause death (HR 1.58, 95% CI 1.50, 1.65). Risks of gallstones, acute cholecystitis and pancreatitis were similar across the classes. Conclusions In patients with type 2 diabetes at risk for gastroparesis, SGLT2i might be the preferred agent. In patients for whom SGLT2i is not an option or another agent is needed, patients and providers might need to weigh the higher risk of death with insulin glargine against the higher risk of gastroparesis with GLP‐1RA.