Association of SGLT2 inhibitors and GLP-1 receptor agonists or DPP-4 inhibitors with incident cancer in patients with type 2 diabetes.

10590 Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) exert potential anti-tumor effects. Emerging data suggest SGLT2i are associated with reduced cancer incidence in type 2 diabetes (T2D), while incretin-based therapies show mixed results varying by cancer type. Among patients with T2D, we tested that hypothesis that use of SGLT2i, as compared to GLP-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), would be associated with lower risk of overall and individual cancer types. Methods: Matched cohort study using MarketScan US claims database (2016–2022). T2D patients with ≥1 metformin prescription and >90 days enrollment before 2 nd line therapy initiation were included. SGLT2i users were matched with up to 5 users of other therapies by age, sex, enrollment, and 2 nd line therapy initiation dates. ICD codes were used to identify cancer. Cox models adjusted for demographics, comorbidities, and medications. Results: Among 365,494 matched patients (mean±SD age 54.2±10.0 years, 48.5% female), 5,422 incident cancers occurred over median 1.43 (maximum 6.75) years follow-up. Cohort included 133,210 SGLT2i users (empagliflozin 55%, dapagliflozin 32%, canagliflozin 12%) and 232,284 comparators (GLP-1RA 60.4%, DPP-4i 39.6%). SGLT2i users showed modestly lower composite cancer risk versus other therapy users Hazard ratio (HR) 0.94, 95% CI 0.89-0.99. Compared with DPP-4i use, SGLT2i use demonstrated 10% lower cancer risk (HR 0.90, 95% CI 0.85-0.97), but showed no significant difference versus GLP-1RA use (HR 0.97, 95% CI 0.91-1.04). Analyses by cancer type revealed no significant differences in HR for breast (0.92, 0.84-1.04), prostate (0.96, 0.84-1.08), colorectal (0.96, 0.82-1.12), lung (0.95, 0.78-1.16), pancreatic (1.04, 0.84-1.28), hepatocellular (1.01, 0.76-1.33), renal cell (0.92, 0.76-1.11), endometrial (1.01, 0.79-1.29), or thyroid cancers (0.84, 0.66-1.06). Cancer risk was comparable across individual SGLT2i(p>0.05). Conclusions: SGLT2i demonstrated a 10% reduction in overall cancer risk versus DPP-4i and comparable efficacy to GLP-1RA, reinforcing SGLT2i's potential oncologic benefits. No associations were observed with individual cancer types, though interpretation is nuanced due to poor precision and short follow-up. Comparable risk among individual SGLT2i suggest a class-wide effect. Future prospective studies with extended follow up are needed to validate these associations and clarify whether SGLT2i offer meaningful cancer risk reduction beyond their established cardiometabolic benefits. Hazard ratios (95% CI) for incident cancer, Marketscan databases, 2016-2022. N (events / total) HR (95% CI) SGLT2i vs. DPP-4i SGLT2i 1,559 / 93,494 0.90 (0.85 - 0.97) DPP-4i 1,749 / 93,494 Ref SGLT2i vs. GLP-1RA SGLT2i 1,699 / 123,955 0.97 (0.91 - 1.04) GLP-1RA 1,757 / 123,955 Ref