Which new diabetes drugs pose risk of digestive diseases?

The study showed that neither dipeptidyl peptidase-4 inhibitors (DPP4is) nor sodium-glucose cotransporter-2 inhibitors (SGLT2is) are associated with several kinds of digestive disease. GLP1RAs were shown to be associated with a higher risk of 4 types of digestive disorders (pancreatitis, gastric ulcer hemorrhage, cholecystitis acute, and cholangitis acute).

New hypoglycemic agents for diabetes treatment are divided into three classes: GLP1R agonists such as semaglutide and liraglutide, SGLT2 inhibitors such as empagliflozin and canagliflozin, and DPP4 inhibitors such as linagliptin and sitagliptin. GLP1RAs and SGLT2is can also exert renal and cardiovascular protection effects. The relation between each class of these new hypoglycemic drugs and the risk of several digestive system diseases remains unknown. Therefore, Cui-Shan Yang, Shenzhen Longhua District Central Hospital, Shenzhen, China, and colleagues aimed to explore this relationship by conducting a meta-analysis.

The study included large randomized trials of GLP1RAs, SGLT2is, and DPP4is. Outcomes included 91 kinds of digestive diseases, including 16 types of hepatobiliary disorders and 75 kinds of gastrointestinal disorders. Pooled risk ratio (RR) was generated. Subgroup analysis was performed per 3 different drug classes. Twenty-one large trials were included in this meta-analysis.

Following were the study's main findings:

• GLP1RAs compared with placebo were associated with higher risks of gastric ulcer bleeding (RR 2.68), cholangitis acute (RR 5.96), pancreatitis (RR 1.48), and cholecystitis acute (RR 1.52) but were not notably associated with the occurrences of the other 87 types of digestive diseases.
• SGLT2is versus placebo was not significantly associated with the occurrences of 91 kinds of digestive diseases.
• DPP4is versus placebo was not significantly associated with the occurrences of 91 kinds of digestive diseases.

The critical limitation of the meta-analysis was the limited number of occurrences of several digestive diseases, to a large extent attenuating this study's statistical power.

"These results seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases whereas DPP4is and SGLT2is are safe for patients susceptible to digestive diseases," the researchers wrote. "However, there is a need for further verification of the findings by future studies with sufficient statistical power."

Reference:

Wang, Yu-Wen MDa,b,*; Lin, Jin-Hao BSc; Yang, Cui-Shan BSb. Meta-analysis of the association between new hypoglycemic agents and digestive diseases. Medicine: August 26, 2022 - Volume 101 - Issue 34 - p e30072 doi: 10.1097/MD.0000000000030072