Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Canagliflozin Increases Intestinal Adenoma Burden in Female ApcMin/+ Mice.

Authors: Korfhage, Justin; Skinner, Mary E; Basu, Jookta; Greenson, Joel K; Miller, Richard A; Lombard, David B

Published In J Gerontol A Biol Sci Med Sci, (2022 02 03)

Abstract: The diabetes drug canagliflozin extends life span in male mice. Since malignant neoplasms are the major cause of death in most mouse strains, this observation suggests that canagliflozin might exert anti-neoplastic effects in male mice. Here, we treated a mouse neoplasia model, the adenoma-prone ApcMin/+ strain, with canagliflozin, to test the effects of this drug on intestinal tumor burden. Surprisingly, canagliflozin increased the total area of intestine involved by adenomas, an effect most marked in the distal intestine and in female mice. Immunohistochemical analysis suggested that canagliflozin may not influence adenoma growth via direct SGLT1/2 inhibition in neoplastic cells. Our results are most consistent with a model where canagliflozin aggravates adenoma development by altering the anatomic distribution of intestinal glucose absorption, as evidenced by increases in postprandial GLP-1 levels driven by delayed glucose absorption. We hypothesize that canagliflozin exacerbates adenomatosis in the ApcMin/+ model via complex, cell-non-autonomous mechanisms, and that sex differences in GLP-1 responses may in part underlie sexually dimorphic effects of this drug on life span.

PubMed ID: 34448851 Exiting the NIEHS site

MeSH Terms: Adenoma*/drug therapy; Animals; Canagliflozin/pharmacology; Canagliflozin/therapeutic use; Female; Glucagon-Like Peptide 1/pharmacology; Glucose; Intestines; Male; Mice; Sodium-Glucose Transporter 2 Inhibitors*/pharmacology; Sodium-Glucose Transporter 2/pharmacology

Back
to Top