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.
Ugwu et al. (Sat,) studied this question.