All-Cause Mortality and Gastrointestinal Adverse Effects in Adults With Type 2 Diabetes on Glucagon-Like Peptide-1 Receptor Agonists vs Sodium–Glucose Cotransporter-2 Inhibitors

Sep 8, 2025Gastro hep advances

Death rates and digestive side effects in adults with type 2 diabetes taking GLP-1 receptor drugs versus SGLT2 inhibitors

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Abstract

Among 104,947 adults with type 2 diabetes treated with GLP-1 receptor agonists, the odds of being diagnosed with gastroparesis and gastroesophageal reflux disease were higher compared to those treated with sodium-glucose cotransporter-2 inhibitors.

Patients on GLP-1RA had an adjusted odds ratio (aOR) of 1.24 for gastroparesis and 1.14 for gastroesophageal reflux disease compared to those on SGLT-2i.
The risk of acute pancreatitis was lower in the GLP-1RA group.
All-cause mortality at 24 months was reduced by 17% in patients treated with GLP-1RA.

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BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly used in adults with type 2 diabetes (T2D), with or without obesity. The incidence of gastrointestinal (GI) adverse effects (AEs) of GLP-1RA in T2D is unclear. This study aimed to evaluate all-cause mortality and GI AEs in T2D patients treated with GLP-1RA compared to those treated with sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

METHODS: A retrospective cohort study used electronic health records from the TriNetX Multi-Institutional Database (January 1, 2021, to December 31, 2022). T2D patients on GLP-1RA were compared to those on SGLT-2i. Primary outcomes were incident GI AEs and all-cause mortality. 1:1 propensity score matching was performed to reduce confounding, and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for each outcome.

RESULTS: The study included 3.2 million adults with T2D, with 104,947 prescribed a GLP-1RA compared with a matched cohort prescribed a SGLT-2i. After matching, baseline characteristics were similar, with a mean age of 62 ± 12 years and mean glycated hemoglobin of 8.0 ± 2.0%. About 30% of participants were from under-represented minority groups. At 24-month follow-up, patients prescribed a GLP-1RA had higher odds of being diagnosed with gastroparesis (GP) and gastroesophageal reflux disease (GERD) compared those prescribed a SGLT-2i, with aORs of 1.24 (95% CI, 1.11-1.38) for GP and 1.14 (95% CI, 1.11-1.18) for GERD. The risk of acute pancreatitis was lower in the GLP-1RA group. All-cause mortality at 24 months had an odds ratio of 0.83 (95% CI: 0.80, 0.87) compared to SGLT-2i.

CONCLUSION: After 24 months of follow-up, patients treated with a GLP-1RA had higher odds of GP and GERD compared to those treated with a SGLT-2i. However, the odds of acute pancreatitis were lower in the GLP-1RA group. All-cause mortality was reduced by 17% in the GLP-1RA group.

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All-Cause Mortality and Gastrointestinal Adverse Effects in Adults With Type 2 Diabetes on Glucagon-Like Peptide-1 Receptor Agonists vs Sodium–Glucose Cotransporter-2 Inhibitors

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