Liraglutide may be associated with increased skin cancer risk: A propensity score-matched analysis.

Abstract

e21504 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used for type 2 diabetes (T2DM) and obesity but long-term oncologic safety data remain limited. In the LEADER trial, liraglutide-treated participants had numerically higher skin cancer rates than placebo. Later studies have yielded mixed results and largely evaluated GLP-1 RAs as a class. In this study, we aimed to evaluate agent-specific associations between individual GLP-1 RAs and skin cancer risk. Methods: Using the TriNetX Global network, we conducted a retrospective cohort study of adults aged ≥18 years with T2DM who was started on an FDA-approved GLP-1 RA (dulaglutide, exenatide, liraglutide, or semaglutide) or a comparator therapy (DPP-4 inhibitor [DPP-4i], SGLT2 inhibitor [SGLT2i], sulfonylurea, or thiazolidinedione [TZD]) between 2015-2020. Patients with a prior history of cancer were excluded. Propensity score matching was performed to balance baseline demographics, comorbidities, and medications. Primary outcome was the incidence of any predefined skin cancer (melanoma, squamous cell carcinoma [SCC], or basal cell carcinoma [BCC]) within 5 years from treatment initiation. Secondary outcomes included the incidence of each individual skin cancer subtype. Results: After propensity score matching, cohort sizes ranged from 14,802 to 59,748. Liraglutide was associated with a modestly higher melanoma risk across multiple active comparators and a higher total skin cancer risk versus SGLT2i (Table 1). No consistent association was observed with BCC, and SCC risk was lower versus DPP4i (Table 1). Dulaglutide, exenatide, and semaglutide were otherwise not associated with a statistically significant change in total skin cancer risk or individual subtypes, except for dulaglutide versus SGLT2i, which showed higher total skin cancer risk (HR 1.19; 95% CI 1.06–1.34). Conclusions: In this study, most GLP-1 RAs were not uniformly associated with risk of total skin cancer or major skin cancer subtypes. However, liraglutide was associated with a higher risk of melanoma across multiple active comparators. These findings suggest agent-specific heterogeneity in skin cancer risk within the class. Further studies are needed to validate these findings. Hazard ratios with 95% confidence intervals for each liraglutide comparison after propensity score matching. Comparison Total skin cancer Melanoma BCC SCC Liraglutide vs DPP4i 1.09 (0.99–1.21) 1.38 (1.09–1.75) 1.11 (0.85–1.47) 0.68 (0.49–0.96) Liraglutide vs SGLT2i 1.15 (1.02–1.29) 1.50 (1.13–1.99) 1.12 (0.81–1.56) 1.08 (0.70–1.66) Liraglutide vs Sulfonylurea 1.07 (0.95–1.20) 1.36 (1.04–1.79) 0.96 (0.71–1.28) 0.82 (0.54–1.24) Liraglutide vs TZD 1.11 (1.00–1.23) 1.35 (1.04–1.76) 1.00 (0.75–1.34) 0.85 (0.59–1.21)