Association of GLP-1 receptor agonists, SGLT 2 inhibitors, DPP-4 inhibitors, and sulfonylureas with incident cancer in type 2 diabetes.

Authors

Stacey M Sklepinski, Jeph Herrin, Kavya Sindhu Swarna, Joshua J Neumiller, Rodolfo J Galindo, Guillermo E Umpierrez, Joseph S Ross, Yihong Deng, Eric C Polley, Mindy M Mickelson, Rozalina G McCoy

Published in

Diabetes research and clinical practice. Pages 113503. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

Limited evidence exists regarding cancer risk associated with non-metformin glucose-lowering medication classes, particularly among obesity-related and obesity-nonrelated cancers.
We compared cancer risk following initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), or sulfonylureas by emulating a target trial using claims data from Optum Labs Data Warehouse and traditional Medicare (100% sample) among adults with type 2 diabetes and moderate cardiovascular risk between January 2014 and December 2021. Random treatment assignment was emulated using propensity scores, which were incorporated as inverse probability of treatment weights into proportional hazard models. Primary outcome was any new cancer diagnosis; we secondarily examined cancer subgroups.
After inverse probability of treatment weighting, 41,123 patients started glucagon-like peptide-1 receptor agonists, 54,423 started sodium-glucose cotransporter 2 inhibitors, 73,803 started dipeptidyl peptidase-4 inhibitors, and 186,988 started sulfonylureas. GLP-1RA were associated with higher risk of new cancer diagnosis compared to DPP4i (HR 1.13, 95%CI 1.05-1.21). SGLT2i (HR 0.89, 95%CI 0.82-0.96) and sulfonylureas (HR 0.87, 95%CI 0.81-0.92) had lower risks of cancer compared to GLP-1RA. Results were driven by obesity-nonrelated cancers.
The increased risk of obesity-nonrelated cancers following GLP-1RA therapy warrants further investigation and caution among at-risk individuals.

PMID:
42607727
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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