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Peer-reviewedCC BY-NC-NDDiabetes research and clinical practice

Association of GLP-1 Receptor Agonists, SGLT 2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas with Incident Cancer in Type 2 Diabetes

  • Stacey M. Sklepinski1
  • Jeph Herrin2
  • Kavya Sindhu Swarna3,4
  • Joshua J. Neumiller5,6
  • Rodolfo J. Galindo7
  • Guillermo E. Umpierrez8
  • Joseph S. Ross9,10
  • Yihong Deng3,4
  • Eric C. Polley11
  • Mindy M. Mickelson3
  • Rozalina G. McCoy4,12,13
13 affiliations
  1. 1University of Maryland School of Medicine, 655 W. Baltimore St, Baltimore, MD 21201, USA
  2. 2Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA
  3. 3Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA
  4. 4Optum Labs, 1 Optum Circle, Eden Prairie, MN 55344, USA
  5. 5Department of Pharmacotherapy, Washington State University, 412 East Spokane Falls Blvd., PBS 130, Spokane, WA 99202-2131, USA
  6. 6Providence Medical Research Center, 105 W 8th Ave, Suite 250E, Spokane, WA 99204, USA
  7. 7Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA
  8. 8Division of Endocrinology, Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA
  9. 9Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA
  10. 10Department of Health Policy and Management, Yale School of Public Health, 60 College St, New Haven, CT 06510, USA
  11. 11Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave MC2000, Chicago, IL 60637, USA
  12. 12Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, 670 W. Baltimore St, Baltimore, MD 21201, USA
  13. 13University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA
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Abstract

AIMS: Limited evidence exists regarding cancer risk associated with non-metformin glucose-lowering medication classes, particularly among obesity-related and obesity-nonrelated cancers. METHODS: 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. RESULTS: After inverse probability of treatment weighting, 41,123 patients started GLP-1RA, 54,423 started SGLT2i, 73,803 started DPP4i, 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, with no difference between study drugs for obesity-related cancers. CONCLUSIONS: The increased risk of obesity-nonrelated cancers following GLP-1RA therapy warrants further investigation and caution among at-risk individuals.

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Cite

BibTeXRIS
BibTeX
@article{sklepinski2026association,
  title = {{Association of GLP-1 Receptor Agonists, SGLT 2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas with Incident Cancer in Type 2 Diabetes}},
  author = {Stacey M. Sklepinski and Jeph Herrin and Kavya Sindhu Swarna and Joshua J. Neumiller and Rodolfo J. Galindo and Guillermo E. Umpierrez and Joseph S. Ross and Yihong Deng and Eric C. Polley and Mindy M. Mickelson and Rozalina G. McCoy},
  journal = {Diabetes research and clinical practice},
  year = {2026},
  month = aug,
  doi = {10.1016/j.diabres.2026.113503},
  url = {https://doi.org/10.1016/j.diabres.2026.113503},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Association of GLP-1 Receptor Agonists, SGLT 2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas with Incident Cancer in Type 2 Diabetes
AU  - Stacey M. Sklepinski
AU  - Jeph Herrin
AU  - Kavya Sindhu Swarna
AU  - Joshua J. Neumiller
AU  - Rodolfo J. Galindo
AU  - Guillermo E. Umpierrez
AU  - Joseph S. Ross
AU  - Yihong Deng
AU  - Eric C. Polley
AU  - Mindy M. Mickelson
AU  - Rozalina G. McCoy
PY  - 2026
DA  - 2026/08/17
JO  - Diabetes research and clinical practice
DO  - 10.1016/j.diabres.2026.113503
UR  - https://doi.org/10.1016/j.diabres.2026.113503
AB  - AIMS: Limited evidence exists regarding cancer risk associated with non-metformin glucose-lowering medication classes, particularly among obesity-related and obesity-nonrelated cancers. METHODS: 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. RESULTS: After inverse probability of treatment weighting, 41,123 patients started GLP-1RA, 54,423 started SGLT2i, 73,803 started DPP4i, 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, with no difference between study drugs for obesity-related cancers. CONCLUSIONS: The increased risk of obesity-nonrelated cancers following GLP-1RA therapy warrants further investigation and caution among at-risk individuals.
SN  - 0168-8227
SN  - 1872-8227
ER  -