SGLT2 inhibitors and outcomes in pancreatic cancer: A large-scale propensity-matched cohort study.

Abstract

687 Background: Pancreatic cancer (PC) carries high mortality and limited therapeutic options. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1a), used for diabetes, exhibit preclinical antitumor effects. Their clinical impact when initiated after PC diagnosis is unclear. Methods: We conducted a retrospective propensity score–matched (PSM) cohort study using the TriNetX US Collaborative Network (71 healthcare organizations, 2010–2022). Two analyses were performed: (1) GLP-1a vs SGLT2i: PC patients receiving GLP-1a after diagnosis (n=1,138) were compared with SGLT2i users (n=2,666); after 1:1 PSM, 1,022 pairs were analyzed (mean age 70 years, 50% female). (2) SGLT2i vs no GLP-1a/SGLT2i: PC patients on SGLT2i post-diagnosis (n=2,666) were compared with those without either drug (n=57,645); after PSM, 1,762 pairs were analyzed (mean age 73.5 years, 41% female). The index event was first prescription after PC diagnosis. Outcomes over 3 years included all-cause mortality (primary), hospitalization, venous thromboembolism (VTE), acute kidney injury (AKI), chronic kidney disease (CKD), and postoperative infection/sepsis. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: In the GLP-1a vs SGLT2i analysis, mortality did not differ significantly (23.4% vs 26.3%; OR 0.86, 95% CI 0.70–1.05; HR 0.90, 95% CI 0.76–1.08). Survival probability at 3 years was 68.9% vs 63.8%. Risks of hospitalization, sepsis, VTE, and AKI were similar, while CKD was more frequent with GLP-1a (10.0% vs 7.0%; OR 1.48, 95% CI 1.03–2.12). In the SGLT2i vs no-drug analysis, SGLT2i was associated with reduced mortality (32.0% vs 48.2%; OR 0.51, 95% CI 0.44–0.58; HR 0.57, 95% CI 0.51–0.63; P<0.001), with higher 3-year survival (58.0% vs 40.8%). SGLT2i also lowered hospitalization (46.7% vs 53.1%; OR 0.77, 95% CI 0.61–0.98), sepsis (15.4% vs 20.3%; OR 0.71, 95% CI 0.59–0.86), and AKI (14.7% vs 20.2%; OR 0.68, 95% CI 0.56–0.83). No significant differences were observed for VTE or CKD. Conclusions: In this large real-world cohort, SGLT2 inhibitors and GLP-1 receptor agonists showed comparable survival when initiated after pancreatic cancer diagnosis, though GLP-1a use was linked to a higher risk of chronic kidney disease. SGLT2 inhibitors, compared with non-users, were associated with significantly lower mortality and improved three-year survival, as well as reduced hospitalization, sepsis, and acute kidney injury. These findings suggest both agents may have clinical relevance, with SGLT2 inhibitors demonstrating broader systemic benefits in PC.