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GLP-1 Receptor Agonists and Risk of Skin Cancer in Adults With Type 2 Diabetes: A Target Trial Emulation

Huilin Tang1,2,3, Bingyu Zhang1,4, Ying Lu1,2

  • 1The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Diabetes, Obesity & Metabolism
|July 28, 2026
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show no increased risk for melanoma. A slight increase in non-melanoma skin cancer (NMSC) risk was noted versus SGLT2is but not after calibration.

Area of Science:

  • Endocrinology and Metabolism
  • Dermatology
  • Pharmacovigilance

Background:

  • Inconclusive evidence links glucagon-like peptide-1 receptor agonists (GLP-1RAs) to melanoma and non-melanoma skin cancer (NMSC) risks.
  • Type 2 diabetes (T2D) patients often use various glucose-lowering medications, necessitating comparative safety assessments.

Purpose of the Study:

  • To evaluate the association between initiating GLP-1RAs and the risks of melanoma and NMSC.
  • To compare these risks against sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) in adults with T2D.

Main Methods:

  • Target trial emulation using TriNetX electronic health records (2014-2025).
  • Inclusion of T2D adults initiating GLP-1RAs, SGLT2is, or DPP4is.
  • Propensity score matching and Cox models to estimate hazard ratios (HRs) for melanoma and NMSC over 3 years, with sensitivity analyses.

Main Results:

  • GLP-1RA initiation was not associated with melanoma risk compared to SGLT2is (HR 1.04) or DPP4is (HR 1.09).
  • A borderline increased risk of NMSC was observed with GLP-1RAs versus SGLT2is (HR 1.06), but not versus DPP4is (HR 1.03).
  • Sensitivity analyses, including negative control outcome calibration, generally supported these findings, attenuating the NMSC association.

Conclusions:

  • GLP-1RA therapy is not linked to an elevated risk of melanoma in T2D patients.
  • A potential borderline increase in NMSC risk versus SGLT2is was observed but not confirmed after calibration, suggesting no significant association.
Keywords:
GLP‐1 analoguecohort studyincretin therapypharmaco‐epidemiologytype 2 diabetes

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