Metformin Use and Long-term Outcomes Including Aneurysm Sac Dynamics Following EVAR for Infrarenal Abdominal Aortic Aneurysm: “A Retrospective Study”

Purpose: Metformin, widely used for the treatment of diabetes mellitus (DM), has shown potential for inhibiting abdominal aortic aneurysm (AAA) growth by reducing extracellular matrix remodeling and inflammation. However, its influence on clinical outcomes and aneurysm sac dynamics after endovascular aneurysm repair (EVAR) remains uncertain. This retrospective study aims to explore the effects of metformin on long-term outcomes following EVAR. Materials and Methods: Patients who underwent elective standard EVAR for infrarenal AAA at a single academic Dutch hospital from 2000 to 2022 were included. We collected baseline patient demographics, comorbid conditions, anatomical and operative characteristics, and 30-day postoperative events. Metformin use was defined as using it preceding EVAR. The primary outcome, the postoperative aneurysm sac volume over time, was investigated using linear mixed-effects modeling. The secondary outcomes, 8-year all-cause mortality and freedom from graft-related events, were evaluated using Kaplan-Meier methods. Results: We analyzed 685 patients, including 634 (93%) non-metformin users and 51 (7%) metformin users. The median follow-up period was similar (4.0 years IQR=1.5, 6.5 vs 5.0 years IQR=2.0, 8.0; p=0.091). Patients on metformin had a preoperative aneurysm sac volume of 153 cc (IQR=114, 195) compared with 178 cc (IQR=133, 240) for non-metformin patients (p=0.054). At 30 days post-EVAR, metformin patients had a comparable mean aneurysm sac volume compared with non-metformin patients (metformin: –19.4 cc 95% confidence interval [CI: –47.4, 8.5]; p=0.173). The effect of metformin on aneurysm growth over time was not significant (–3.9 cc/year; 95% CI: –22.7, 14.9; p=0.685). Following risk-adjusted analysis, metformin use was associated with similar rates of all-cause mortality (metformin vs no metformin: 50% vs 44%; hazard ratio HR=1.11, 95% CI: 0.66, 1.88; p=0.688) and freedom from graft-related events (metformin vs no metformin: 63% vs 66%; HR=1.82, 95% CI: 0.98, 3.38; p=0.059). Conclusion: Although metformin use may reduce preoperative AAA growth, it does not seem to influence overall/long-term post-EVAR AAA sac dynamics, all-cause mortality, or freedom from graft-related events. These findings suggest that the potential protective effect of metformin on AAA may not be sustained after EVAR. Further prospective studies are needed to investigate the mechanisms underlying the potential role of metformin in AAA management following EVAR. Clinical Impact There is currently no approved pharmacological treatment available to slow the abdominal aortic aneurysm (AAA) growth rate and reduce the related risk of rupture. In our retrospective analysis including 685 patients undergoing EVAR for infrarenal AAA, we found that metformin use was not associated with improved post-EVAR outcomes, such as a reduction of aneurysm sac volume over time, eight-year all-cause mortality, or freedom of graft-related events. These findings suggest that the potential protective effect of metformin on AAA may not be sustained after EVAR and underscore the need for ongoing research into this area.