Gastrointestinal and Hepatobiliary Safety of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes
Bibliographic record
Abstract
INTRODUCTION: To evaluate the long-term gastrointestinal (GI) and hepatobiliary safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus, compared with other oral antidiabetic medications. METHODS: A retrospective cohort study using the TriNetX network was conducted between 2010 and 2020. After 1:1 propensity score matching, 230,415 patients were included in each group (GLP-1 RAs vs oral antidiabetes mellitus medications). Hazard ratios (HRs) for GI and hepatobiliary outcomes were assessed over 5 years. RESULTS: Among 230,415 matched patients per group, GLP-1 RA use was associated with a higher risk of gastroparesis (HR 1.591, P < 0.001) and intussusception (HR 1.383, P = 0.025) compared with oral antidiabetic therapy. There were no significant differences in acute pancreatitis, cholecystitis, or cholecystectomy rates between groups. Conversely, GLP-1 RA therapy was not associated with increased incidence of GI cancers. Lower hazard ratios were observed for pancreatic (HR 0.897, P = 0.038), gastric (HR 0.838, P = 0.034), esophageal (HR 0.741, P = 0.001), and colorectal cancer (HR 0.870, P = 0.001), although causality cannot be inferred. No significant differences were observed in biliary cancer or hepatocellular carcinoma. DISCUSSION: In this large real-world cohort study, GLP-1 RA therapy was not associated with increased risk of most serious GI or hepatobiliary outcomes compared with other oral diabetes medications. These findings support the overall GI and hepatobiliary safety of GLP-1 RAs in patients with type 2 diabetes, while underscoring the need for vigilance regarding gastroparesis and intussusception in susceptible individuals. Longer-term studies are warranted to fully evaluate cancer risk.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".