Introduction
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing colorectal adenomas and cancer. Newer medications such as sodium-glucose cotransporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are increasingly used in DM patients with promising results on improving glycaemic control and other outcomes. While studies showed that the use of GLP-1 RA could affect intestinal transit time and bowel preparation quality, their effect on adenoma detection remains unclear.
Aims & Methods
This population-based retrospective cohort study included all adult T2DM patients who were prescribed with either GLP-1 RA or SGLT2 inhibitors for more than 180 days, and had undergone colonoscopy between 2018 and 2024 in Hong Kong. Anonymous patient’s data were retrieved from the territory-wide electronic medical system (CDARS). We excluded patients with history of previous colonoscopy or were on both medications. The primary outcome was proportion of patients with adenoma detected (ADR) during colonoscopy in GLP-1 versus SGLT2 group. GLP-1 RA use was treated as a time-varying variable to address immortal-time bias. Multivariable Cox regression model with adjusted hazard ratio (aHR) was used as primary analysis, which adjusted for patient’s age and sex, smoking and drinking status, body mass index, colonoscopy’s quality (bowel preparation, scope withdrawal time and indications), time-weighted mean HbA1c, concurrent illnesses (hypertension, stroke, ischemic heart disease, chronic renal disease and chronic liver disease), medication uses (dipeptidyl peptidase 4, insulin, metformin, pioglitazone, statin, sulfonylurea, proton pump inhibitor). Propensity-score matching (PSM) with 1:2 match was used as secondary analysis.
Results
There was a total of 12,789 DM patients who had colonoscopy during the study period (977 on GLP-1 RA and 11812 on SGLT2). Among them, 6192 (48.4%) patients were found to have adenomas during colonoscopy (GLP-1 38.3% and SGLT2 49.2%). In the time-dependent analysis, GLP-1 group was found to have a significantly lower ADR when compared to SGLT2 group (aHR: 0.40; 95% CI 0.36–0.45; P<0.01). In the PSM cohort (1:2 match), all covariates were well matched with absolute standardized mean difference < 0.1. PSM analysis showed a similar finding with aHR: 0.38 (95% CI 0.33–0.43; P<0.01; Table 1). There was a duration-response relationship with longer GLP-1 use duration linked to greater reduction in ADR (<1 year: aHR 0.71, 95% CI 0.60–0.84; 1–<2 years: aHR 0.51, 95% CI 0.43–0.61; ≥2 years: aHR 0.33, 95% CI 0.28–0.38; P-trend<0.01). Consistent lower ADRs were observed across different levels of bowel preparation quality (from BBPS 3 to 9) in GLP-1 group with HRs of 0.37–0.45 (p ≤ 0.01). Subgroup analysis showed similar results across most demographics, clinical factors, and comorbidities (HRs 0.34–0.44, p < 0.01), except in subgroups with short scope withdrawal time.
Table 1. Association between GLP-1 RA use with ADR
Primary outcome of interest— Detection of adenoma
| ADR
| Adjusted HR (95% CI)
| P values
|
Main analysis (time-dependent analysis)*
SGLT2-I users
GLP-1 RA users
|
49.3% (5818/11812)
38.3% (374/977)
|
Ref
0.40(0.36-0.45)
|
<0.01 |
Secondary analysis (PSM analysis)
SGLT2-I users
GLP-1 RA users
|
46.7% (912/1954)
38.3% (374/977)
|
Ref
0.38(0.33-0.43)
|
<0.01 |
Conclusion
DM patients who use GLP-1 RA are found to have a lower rate of adenoma detected during colonoscopy than those who use SGLT-2 in this population-based study. The results remain similar even after stratified according to different levels of bowel preparation quality. These findings may suggest a potential protective role of GLP-1 receptor agonists against colorectal adenoma development, which warrant further prospective study to confirm.
