Short-Acting GLP-1 RAs May Increase GERD, Barrett Esophagus Risk in Type 2 Diabetes

Short-acting glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) are associated with increased risk for developing gastroesophageal reflux disease (GERD) and its associated complications, according to study results presented at Digestive Disease Week (DDW), held from May 6 to 9, 2023 in Chicago, Illinois, and virtually.

Both short- and long-acting GLP-1 RAs are used for the treatment of type 2 diabetes (T2D). These drugs cause delayed gastric emptying, which is a known risk factor for GERD.

This study was designed to evaluate whether GLP-1 RAs may be related with GERD risk. Investigators from the MetroHealth Medical Center in the United States sourced data for this study from the TriNetX database, which includes electronic health records from 91 health care organizations in 12 countries. Patients (n=341,829) who had T2D at the time of GLP-1 RA initiation between 2002 and 2022 were propensity-matched with patients who initiated sodium-glucose co-transporter 2 inhibitors (SGLT2i; n=265,181). The 2 groups were evaluated for new diagnoses of GERD, GERD reflux esophagitis (GERDre), esophageal stricture, Barrett esophagus, use of proton pump inhibitors (PPIs), and undergoing esophagogastroduodenoscopy (EGD) during a 3-year follow-up.

The prematched GLP-1 RA and SGLT2i cohorts included patients with a mean [SD] of 57.4[12.8] and 61.1[12] years; 57.8% and 40.7% were women; 66.0% and 65.3% were White; they had a BMI of 35.9[7.0] and 32.8[6.7] kg/m²; glycated hemoglobin of 8.29%[2.12%] and 8.19%[1.93%]; 62.2% and 64.8% had hypertension; and, 44.0% and 47.5% had hyperlipidemia, respectively.

Among the propensity matched groups (n=233,774 in each), the GLP-1 RA cohort was associated with GERD (odds ratio [OR], 1.32; 95% CI, 1.29-1.36), GERDre (OR, 1.19; 95% CI, 1.12-1.26), esophageal stricture (OR, 1.19; 95% CI, 1.07-1.32), Barrett esophagus (OR, 1.25; 95% CI, 1.12-1.39), new PPI use (OR, 1.32; 95% CI, 1.29-1.36), and undergoing EGD (OR, 1.31; 95% CI, 1.20-1.44).

Stratified by short- (n=113,533) and long- (n=193,376) acting GLP-1 RAs, the patients who used short-acting GLP-1 RAs were associated with increased risk for GERD (OR, 1.73; 95% CI, 1.67-1.79), GERDre (OR, 1.73; 95% CI, 1.60-1.86), esophageal stricture (OR, 1.72; 95% CI, 1.49-1.98), Barrett esophagus (OR, 1.50; 95% CI, 1.30-1.74), new PPI use (OR, 1.57; 95% CI, 1.52-1.63), and undergoing EGD (OR, 1.74; 95% CI, 1.66-1.82) compared with the SGLT2i users.

Long-acting GLP-1 RAs were only associated with GERD (OR, 1.10; 95% CI, 1.07-1.13) and undergoing EGD (OR, 1.08; 95% CI, 1.04-1.12) relative to the SGLT2i cohort.

In subgroup analyses, some evidence suggested that trends were based on glycated hemoglobin levels and BMI at baseline.

Study authors concluded, “Short-acting but not long-acting GLP-1 RA use is an independent risk factor for developing GERD and Barrett’s esophagus in patients with type 2 diabet[es].”