Glucagon-Like Peptide-1 Receptor Agonists and Risk for Gastroesophageal Reflux Disease in Patients With Type 2 Diabetes : A Population-Based Cohort Study.
Level 3 - non-randomized controlled study
Active-comparator new-user cohort study emulating a target trial
PubMed 40658955 · doi:10.7326/ANNALS-24-03420
What was done
An active-comparator new-user cohort study emulating a target trial was conducted using the U.K. Clinical Practice Research Datalink. The study included adults (aged ≥18 years) with type 2 diabetes who initiated either a GLP-1 receptor agonist (n = 24,708) or an SGLT-2 inhibitor (n = 89,096) between January 1, 2013, and December 31, 2021, with follow-up through March 31, 2022. The primary outcome was incident GERD, and the secondary outcome was GERD complications. Outcomes were weighted using propensity score fine stratification to estimate 3-year risk differences (RDs) and risk ratios (RRs).
What was found
Over a median follow-up of 3.0 years, GLP-1 RA users had a higher risk compared with SGLT-2 inhibitor users for: - Incident GERD: RR 1.27 (95% CI, 1.14 to 1.42), with an RD of 0.7 per 100 patients. - GERD complications: RR 1.55 (95% CI, 1.12 to 2.29), with an RD of 0.8 per 1000 patients.
Why it matters
This study provides large-scale real-world evidence confirming that GLP-1 RA use is associated with an elevated risk of GERD and related complications compared to SGLT-2 inhibitors, informing clinical monitoring and risk-benefit discussions in type 2 diabetes management.
Limits
The study is subject to potential residual confounding due to a lack of data on lifestyle and dietary factors. It relied on routinely recorded primary care data, which may miss unrecorded or self-managed symptoms. Findings are restricted to individuals with type 2 diabetes compared against SGLT-2 inhibitor users and may not directly generalize to non-diabetic populations using GLP-1 RAs for weight loss.
Cited by
- supports Eating large solid meals close to bedtime while on GLP-1 receptor agonists leads to severe heartburn and gastrointestinal discomfort due to delayed gastric emptying.