Diabetes, obesity & metabolismJul 30, 2025

Blood sugar treatments and the risk of digestive problems in veterans with type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 5, 2026

Abstract

Among 141,080 veterans with type 2 diabetes, 14.0% initiated glucagon-like peptide-1 receptor agonists (GLP-1RA).

GLP-1RA use is associated with a higher risk of compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i) and insulin glargine.
Compared to SGLT2i, the hazard ratio for gastroparesis with GLP-1RA is 1.65.
Compared to insulin glargine, GLP-1RA also shows a higher hazard of gastroparesis with a hazard ratio of 1.24.
GLP-1RA is associated with a lower risk of all-cause death compared to insulin glargine, with a hazard ratio of 0.62.
Insulin glargine has a higher risk of all-cause death and intestinal obstruction compared to SGLT2i.
The risks of gallstones, acute cholecystitis, and pancreatitis are similar across GLP-1RA, SGLT2i, and insulin glargine.

Simplified

AIMS: To compare the risk of gastrointestinal adverse events in new users of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and insulin glargine.

MATERIALS AND METHODS: We conducted an active comparator, new user design study in veterans with type 2 diabetes who initiated one of these drug classes between 1 January 2018 and 31 December 2021 (N = 141 080). Inverse probability weighted Cox regression models were used to relate drug class to outcomes of , intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis and all-cause death.

RESULTS: There were 19 765 (14.0%) veterans initiated on GLP-1RA, 75 058 (53.2%) on SGLT2i and 46 257 (32.8%) on insulin glargine. Compared to SGLT2i, GLP-1RA had a higher hazard of gastroparesis (HR 1.65, 95% CI 1.33-2.05) but a similar mortality hazard. Compared to insulin glargine, GLP-1RA had a higher hazard of gastroparesis (HR 1.24, 95% CI 1.02, 1.52), but a lower hazard of all-cause death (HR 0.62, 95% CI 0.58, 0.66). Compared to SGLT2i, insulin glargine had a higher hazard of gastroparesis (HR 1.29, 95% CI 1.07, 1.56), intestinal obstruction (HR 1.26, 95% CI 1.11, 1.43) and all-cause death (HR 1.58, 95% CI 1.50, 1.65). Risks of gallstones, acute cholecystitis and pancreatitis were similar across the classes.

CONCLUSIONS: In patients with type 2 diabetes at risk for gastroparesis, SGLT2i might be the preferred agent. In patients for whom SGLT2i is not an option or another agent is needed, patients and providers might need to weigh the higher risk of death with insulin glargine against the higher risk of gastroparesis with GLP-1RA.

Key numbers

1.65

Higher Risk of with GLP-1RA

Hazard ratio compared to SGLT2i

1.58

Higher Risk of All-Cause Death with Insulin Glargine

Hazard ratio compared to SGLT2i

141080

Cohort Size

Total number of veterans included in the study

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Funding

Competing interests

SB received research support from Bayer, Novo Nordisk and Boehringer Ingelheim. SD is a consultant with Abbott and receives research support from Novartis.

PubMed

Blood sugar treatments and the risk of digestive problems in veterans with type 2 diabetes

Abstract

Key numbers

Full Text

Funding

Competing interests

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Abstract

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Competing interests

Related papers

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Recent issues from the glp-1 therapies brief