# Risk of Incident Colorectal Carcinoma in Patients With Type 2 Diabetes on SGLT‐2 Inhibitor Users

## TL;DR

This study found that using SGLT2 inhibitors in patients with type 2 diabetes is linked to a lower risk of developing colorectal cancer.

## Contribution

The study provides population-based evidence that SGLT2 inhibitor use is associated with reduced colorectal cancer risk in type 2 diabetes patients.

## Key findings

- SGLT2I users had a 20% lower risk of CRC compared to nonusers after adjusting for covariates.
- Reduced CRC risk was observed across both sexes and age groups in SGLT2I users.
- The association remained consistent in sensitivity analyses using propensity score matching.

## Abstract

The role of sodium‐glucose co‐transporter‐2 inhibitor (SGLT2I) in colorectal carcinoma (CRC) risk in patients with type 2 diabetes mellitus (T2D) remains controversial. This study aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with T2D.

This nationwide retrospective cohort study was conducted using the National Health Insurance Research Database (2015–2021). The primary outcome was the risk of incident CRC, estimated using hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was conducted to analyze the association between SGLT2I use and incident CRC risk in patients with T2D.

A total of 304 698 SGLT2I users and 609 396 nonusers were matched in a 1:2 ratio by age, sex, and index year from 2 617 996 patients with T2D. Among patients with T2D, 1436 and 3555 incident CRCs were recorded in SGLT2I users and nonusers, respectively. After adjusting for the index year, sex, age, and comorbidities, a significantly decreased risk of CRC was observed among SGLT2I users compared to nonusers (adjusted HR 0.80, 95% CI 0.74–0.85). The sensitivity test for the propensity score 1:1‐matched analyses also showed similar results (adjusted HR 0.79, 95% CI 0.74–0.85).

This population‐based cohort study found that SGLT2I use was associated with a lower risk of CRC than nonuse of SGLT2I in patients with T2D. More studies are needed to evaluate the effects of SGLT2I therapy on CRC prevention in patients with T2D.

The metabolic dysregulation that occurs in diabetes mellitus (DM) may contribute to colorectal carcinoma (CRC) carcinogenesis and proliferation through inflammation and oxidative stress‐driven signaling alterations.Recently, in vitro and in vivo studies have found that sodium‐glucose co‐transporter‐2 inhibitors (SGLT2Is) may reduce CRC risk.This study aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with type 2 DM.SGLT2I use in patients with type 2 DM decreased the risk of CRC. Moreover, lower risks were also observed in both sexes and age groups among SGLT2I users.This study suggests that pharmacological interventions may be beneficial in decreasing the risk of CRC in SGLT2I users.

The metabolic dysregulation that occurs in diabetes mellitus (DM) may contribute to colorectal carcinoma (CRC) carcinogenesis and proliferation through inflammation and oxidative stress‐driven signaling alterations.

Recently, in vitro and in vivo studies have found that sodium‐glucose co‐transporter‐2 inhibitors (SGLT2Is) may reduce CRC risk.

This study aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with type 2 DM.

SGLT2I use in patients with type 2 DM decreased the risk of CRC. Moreover, lower risks were also observed in both sexes and age groups among SGLT2I users.

This study suggests that pharmacological interventions may be beneficial in decreasing the risk of CRC in SGLT2I users.

Why was this study conducted?
○Previous studies have shown that diabetes mellitus is associated with an increased risk of colorectal carcinoma. Recent in vitro and in vivo studies have found that sodium‐glucose co‐transporter‐2 inhibitors (SGLT2I) may reduce the colorectal carcinoma (CRC) risk. We performed a population‐based cohort study using Taiwan's National Health Insurance Research Database from 2014 to 2021. We aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with type 2 diabetes (T2D).
What are the key findings?
○SGLT2I use was associated with a lower risk of CRC than non‐use of SGLT2I in patients with T2D. The lower risks of CRC were also seen in both sexes and age groups in SGLT2I users.
What does this study add to what is already known?
○Pharmacological interventions may be beneficial in decreasing the risk of CRC in SGLT2I users.

Why was this study conducted?
○Previous studies have shown that diabetes mellitus is associated with an increased risk of colorectal carcinoma. Recent in vitro and in vivo studies have found that sodium‐glucose co‐transporter‐2 inhibitors (SGLT2I) may reduce the colorectal carcinoma (CRC) risk. We performed a population‐based cohort study using Taiwan's National Health Insurance Research Database from 2014 to 2021. We aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with type 2 diabetes (T2D).

Previous studies have shown that diabetes mellitus is associated with an increased risk of colorectal carcinoma. Recent in vitro and in vivo studies have found that sodium‐glucose co‐transporter‐2 inhibitors (SGLT2I) may reduce the colorectal carcinoma (CRC) risk. We performed a population‐based cohort study using Taiwan's National Health Insurance Research Database from 2014 to 2021. We aimed to examine the association between SGLT2I use and the risk of incident CRC in patients with type 2 diabetes (T2D).

What are the key findings?
○SGLT2I use was associated with a lower risk of CRC than non‐use of SGLT2I in patients with T2D. The lower risks of CRC were also seen in both sexes and age groups in SGLT2I users.

SGLT2I use was associated with a lower risk of CRC than non‐use of SGLT2I in patients with T2D. The lower risks of CRC were also seen in both sexes and age groups in SGLT2I users.

What does this study add to what is already known?
○Pharmacological interventions may be beneficial in decreasing the risk of CRC in SGLT2I users.

Pharmacological interventions may be beneficial in decreasing the risk of CRC in SGLT2I users.