Comparative risks of inflammatory bowel disease in patients with type 2 diabetes mellitus treated with SGLT-2 inhibitors versus DPP-4 inhibitors: a real-world nationwide cohort study

Oct 21, 2025International journal of clinical pharmacy

Risk of inflammatory bowel disease in type 2 diabetes patients using SGLT-2 inhibitors compared to DPP-4 inhibitors in a nationwide study

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Abstract

Among 258,355 patients, the incidence of inflammatory bowel disease (IBD) was lower in those using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i).

SGLT-2i users experienced an incidence of IBD at 12.51 per 100,000 person-years, while DPP-4i users had an incidence of 35.83 per 100,000 person-years.
SGLT-2i use was associated with a significantly reduced risk of developing IBD, with an adjusted hazard ratio of 0.391.
The findings were consistent across multiple sensitivity analyses, indicating robustness in the association.
The study suggests that SGLT-2i may have gut-protective effects in patients with type 2 diabetes mellitus.

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INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been suggested to exert anti-inflammatory effects in the gastrointestinal tract based on preclinical and observational studies. Whether these effects translate into a reduced risk of inflammatory bowel disease (IBD), compared with other antidiabetic agents of similar therapeutic rank, remains unclear.

AIM: This study aims to evaluate the association between SGLT-2i use and the risk of IBD in patients with type 2 diabetes mellitus (T2DM), using dipeptidyl peptidase-4 inhibitors (DPP-4i) as an active comparator.

METHOD: A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database from 2016 to 2022. Patients with T2DM who initiated SGLT-2i or DPP-4i therapy were included. Propensity score matching (1:4) was performed based on key covariates. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated for incident IBD, including its subtypes ulcerative colitis (UC) and Crohn's disease (CD), using Cox proportional hazards models and Fine and Gray competing risk models (considering death as a competing event), with further adjustment for residual confounding. Sensitivity analyses were conducted using alternative induction periods and several on-treatment approaches that accounted for treatment discontinuation.

RESULTS: Among 258,355 patients (51,671 SGLT-2i users and 206,684 DPP-4i users), the incidence of IBD was lower in the SGLT-2i group (12.51 vs. 35.83 per 100,000 person-years). SGLT-2i use was associated with a significantly reduced risk of IBD (aHR: 0.391; 95% CI 0.237-0.645; p < 0.001), with consistent results across multiple sensitivity analyses.

CONCLUSION: In this nationwide real-world cohort, SGLT-2i use was associated with a lower risk of IBD compared with DPP-4i among patients with T2DM. These findings suggest potential gut-protective effects of SGLT-2i and support their consideration in clinical decision-making for patients at elevated risk of IBD. Further prospective studies are warranted to validate these observations and elucidate the underlying mechanisms.

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Comparative risks of inflammatory bowel disease in patients with type 2 diabetes mellitus treated with SGLT-2 inhibitors versus DPP-4 inhibitors: a real-world nationwide cohort study

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