Incretin‐Based Drugs and Risk of Intestinal Obstruction Among Patients With Type 2 Diabetes

Sep 29, 2021Clinical pharmacology and therapeutics

Incretin-Based Drugs and Risk of Intestinal Blockage in People with Type 2 Diabetes

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Abstract

GLP-1 receptor agonists (GLP-1 RAs) and DPP-4 inhibitors are associated with an increased risk of intestinal obstruction, with rates of 1.9 and 2.7 per 1,000 person-years, respectively.

GLP-1 RAs showed a hazard ratio (HR) of 1.69 for intestinal obstruction compared to SGLT-2 inhibitors.
The highest risk for GLP-1 RA users was noted after 1.6 years, with an HR of 3.48.
DPP-4 inhibitors had a higher HR of 2.59 compared to SGLT-2 inhibitors for intestinal obstruction.
The peak risk for DPP-4 inhibitor users occurred after 1.8 years, with an HR of 9.53.
The number needed to harm after 1 year was 1,223 for GLP-1 RAs and 603 for DPP-4 inhibitors.

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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors might increase the risk of intestinal obstruction, but real-world evidence for this severe adverse event is lacking. Thus, the objective of this study was to determine whether GLP-1 RAs and DPP-4 inhibitors are associated with an increased risk of intestinal obstruction compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We used the United Kingdom Clinical Practice Research Datalink and linked databases to assemble two new-user, active comparator cohorts (2013-2019). The first included 25,617 and 67,261 GLP-1 RA and SGLT-2 inhibitor users, respectively. The second included 131,927 and 40,615 DPP-4 inhibitor and SGLT-2 inhibitor users, respectively. Propensity score fine stratification weighted Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of intestinal obstruction requiring hospitalization. GLP-1 RAs were associated with an increased risk of intestinal obstruction compared with SGLT-2 inhibitors (1.9 vs. 1.1 per 1,000 person-years, respectively; HR: 1.69, 95% CI: 1.04-2.74). The highest HR was observed after 1.6 years of use (HR: 3.48, 95% CI: 1.79-6.79). DPP-4 inhibitors were also associated with an increased risk (2.7 vs. 1.0 per 1,000 person-years; HR: 2.59, 95% CI: 1.52-4.42), with the highest HR observed after 1.8 years of use (HR: 9.53, 95% CI: 4.47-20.30). The number needed to harm after 1 year of use was 1,223 and 603 for GLP-1 RAs and DPP-4 inhibitors, respectively. In this large real-world study, GLP-1 RAs and DPP-4 inhibitors were associated with an increased risk of intestinal obstruction.

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Incretin‐Based Drugs and Risk of Intestinal Obstruction Among Patients With Type 2 Diabetes

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