Comparing mortality risk in patients with malignant melanoma and type 2 diabetes mellitus treated with immunotherapy alone versus immunotherapy plus SGLT2 inhibitors

Muhammad Mujtaba Bhinder; Ammad Naeem; Mohammad Khudayar; Abdullah Sohail; Amir Kamran

doi:10.1200/JCO.2025.43.16_suppl.e14619

e14619 Background: Patients with malignant melanoma (MM) and type 2 diabetes mellitus (T2DM) face treatment challenges due to complex therapy interactions. This study examines whether adding sodium-glucose co-transporter 2 (SGLT2) inhibitors to immunotherapy (pembrolizumab, nivolumab, or ipilimumab) improves survival and reduces mortality. Methods: Using a retrospective cohort design, data from 103 healthcare organizations in the TriNetX Research Network were analyzed. Two matched groups (n=559 each) were compared: immunotherapy alone (IT-only) and immunotherapy plus SGLT2 inhibitors (IT + SGLT2). Propensity score matching ensured comparability. Mortality was the primary outcome, assessed via risk analysis, Kaplan-Meier curves, and hazard ratios. Results: The IT + SGLT2 group had a lower mortality risk (20.4%) than the IT-only group (30.6%; Risk Difference: 10.2%; 95% CI: 5.1%–15.3%; p<0.001). Kaplan-Meier analysis showed higher survival probabilities (58.6% vs. 46.4%; Log-Rank p=0.003). The mortality hazard ratio was 1.427 (95% CI: 1.125–1.810; p=0.241). Conclusions: Adding SGLT2 inhibitors to immunotherapy significantly lowers mortality and improves survival in MM patients with T2DM. These findings highlight their potential to enhance treatment strategies, supported by large-scale data like TriNetX. Further research is needed to validate results and uncover underlying mechanisms for more personalized therapies. Propensity matching of baseline characteristics. Baseline Characteristics Before propensity matching After propensity matching IT only (N=4,021) IT + SGLT2i Group (N=559) P value IT only (N=559) IT + SGLT2i Group (N=559) P value Characteristics: Age, y, mean ± SD 72.7 +/- 11.5 71.2 +/- 10.6 0.002 71.2 +/- 10.5 71.2 +/- 10.6 0.966 Male, n(%) 2,652 (66) 412 (73.7) <0.001 412 (73.7) 412 (73.7) 1.00 Female, n (%) 1,216 (30.2) 128 (22.9) <0.001 131 (23.4) 128 (22.9) 0.83 Race, n (%) White 3,492 (86.8) 497 (88.9) 0.17 501 (89.6) 497 (88.9) 0.70 Black or African American 92 (2.3) 10 (1.8) 0.45 10 (1.8) 10 (1.8) 1.00 Other Race 118 (2.9) 13 (2.3) 0.42 13 (2.3) 13 (2.3) 1.00 Unknown Race 235 (5.8) 33 (5.9) 0.96 272 (18.80%) 302 (20.90%) 0.16 Comorbid Conditions: HTN 3074 (76) 471 (84) <0.01 476 (85.2) 471 (84.3) 0.68 Ischemic heart diseases 1392 (34.6) 242 (43.3) <0.01 239 (42.8) 242 (43.3) 0.86 Malignant neoplasms of ill-defined, other secondary and unspecified sites 2998 (74.6) 411 (73.5) 0.60 416 (74.4) 411 (73.5) 0.73 Benign neoplasms, except benign neuroendocrine tumors 1,785 (44.4) 276 (49.4) 0.03 276 (49.4) 276 (49.4) 1.00 Hemoglobin A1c: 6.9 +/- 1.6; 2135 (53.1) 7.6 +/- 1.7; 378 (67.6) <0.01 7.1 +/- 1.6; 378 (67.8) 7.6 +/- 1.7; 378 (67.6) <0.01 Blood glucose regulation agents 3,031 (75.4) 550 (98.4) <0.001 550 (98.4) 550 (98.4) 1.00 Odds Ratio 1.72 ; 95% CI (1.30 - 2.26) p<0.01 Risk Ratio 1.5; 95% CI ( 1.22 - 1.84 p<0.01

Comparing mortality risk in patients with malignant melanoma and type 2 diabetes mellitus treated with immunotherapy alone versus immunotherapy plus SGLT2 inhibitors

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