Introduction:

Type 2 diabetes mellitus (T2DM) is a common comorbidity in patients with renal cell carcinoma (RCC), with studies estimating that approximately 15% of RCC patients have pre-existing T2DM. Among those undergoing partial nephrectomy, T2DM has been associated with worse prognosis. As antidiabetic medication regimens evolve, previous studies have investigated the correlation of medications, such as metformin and dipeptidyl peptidase IV inhibitors (DPP4i), on postoperative survival rates. However, the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains largely unexplored. GLP-1RAs are widely used in the contemporary management of T2DM and obesity. In addition to their hypoglycemic effects, they have demonstrated potential cardiovascular and renal benefits. Consequently, GLP-1RAs may positively affect postoperative outcomes in T2DM patients with RCC. Therefore, this study investigates the association between GLP-1RAs use and 90-days postoperative adverse outcomes and overall survival in T2DM patients with localized RCC undergoing partial nephrectomy. 

Methods:

The TriNetX database was used to retrospectively identify patients who underwent partial nephrectomy for T1 or T2 RCC between 2005 and 2025 (n = 33,782). Of these, 10,540 were diagnosed with T2DM. Out of 10,540, 5,786 patients were identified as having been prescribed an antidiabetic medication. Patients were categorized based on whether they were prescribed GLP-1 receptor agonists: those who received GLP-1RAs (GLP-1RA group) and those who did not (non-GLP-1RA group). The GLP-1RAs group (n = 957) was 1:1 propensity score matched to the non-GLP-1RAs group (n = 4,829) based on baseline characteristics, comorbidities, metformin prescription, and renal function laboratory values. After matching, 953 patients in each group were yielded. For ninety-day postoperative adverse events, risk difference, risk ratio, and odds ratio with 95% confidence intervals were calculated. Kaplan-Meier analysis and log-rank tests were performed to measure the effect of GLP-1RAs use on overall survival. 

Results:

Of the 5,786 T2DM patients with localized RCC who underwent partial nephrectomy, 957 (16.5%) were prescribed GLP-1RAs. GLP-1RAs use was associated with lower odds of the following 90-days postoperative adverse outcomes: acute kidney injury (odds ratio [OR] = 0.702), pneumonia (OR = 0.492), arrhythmia (OR = 0.713), transfusion (OR = 0.475), and hospitalization (OR = 0.749) compared to non GLP-1RAs group (P < 0.05 for each) (Table 1). After the median follow up period of 2 years for GLP-1RAs group and 3 years for non-GLP-1RAs group, Kaplan-Meier analysis and log rank tests demonstrated improved 2-year ( p = 0.0173) (Figure 1A) and 3-year ( p = 0.0152) (Figure 1B) overall survival among patients prescribed GLP-1RAs compared those who were not.

Conclusion:

This study demonstrates the promising potential of GLP-1RAs in improving overall survival among patients with T2DM and localized RCC. Our findings suggest that the long-term benefits may be attributed to a decreased incidence of 90-day postoperative complications, such as acute kidney injury, pneumonia, arrhythmia, transfusion, and overall hospitalization- potentially contributing to increased overall survival. These results align with ongoing studies investigating the broader benefits of GLP-1RAs use. While these findings underscore the potential benefits of GLP-1RAs use, limitations of this study include its retrospective design and the inability to measure medication adherence and duration. Therefore, further validation through larger prospective studies is warranted. 

Funding: N/A