Reamputation risk and mortality after lower-limb amputation in patients with diabetes: predictors, effects of antidiabetic medications and temporal trends

Abstract Background Diabetes is associated with a high incidence of diabetic foot and peripheral artery disease and with markedly increased lifetime amputation risk. Here we investigated predictors of reamputation risk and mortality including antidiabetic medication in patients undergoing non-traumatic lower limb amputation (LLA). Methods In an observational longitudinal study, we analyzed 607 patients with diabetes and 500 patients without diabetes who underwent non-traumatic LLA between 2006 and 2022. The primary endpoint was reamputation-free survival. Predictors of subsequent amputations or mortality were analyzed using Cox regression and joint frailty models. Results Diabetes was independently associated with increased combined reamputation and mortality risk (HR 1.28, 95% CI [1.08, 1.52], p = 0.004). Reduced reamputation-free survival in patients with diabetes was triggered by a marked higher reamputation risk. Higher HbA1c levels were associated with lower reamputation-free survival. Older age, presence of atrial fibrillation and chronic kidney disease were associated with increased reamputation risk in patients with diabetes. Metformin usage in patients with type 2 diabetes was associated with a marked reduction in combined risk of reamputation and mortality (HR 0.59, 95% CI [0.43, 0.81] p = 0.001). While overall sodium-glucose transporter 2 inhibitor (SGLT2i) usage was low in this cohort, it was associated with an increased reamputation risk (HR 2.00, 95% CI [1.47, 2.72], p > 0.001) although safe with respect to mortality. Over time, reamputation risk peaked between 2020 and 2022, whereas mortality declined compared with the period from 2006 to 2010 in patients with diabetes. Conclusion Diabetes remains to be associated with reduced reamputation-free survival; an association that is independent of increased prevalence of comorbidities in our data. Although reamputation risk has increased in recent years, overall survival has improved in patients with diabetes. Metformin usage is associated with improved reamputation-free survival while our limited data suggest increased risk of reamputation but safety with respect to mortality in patients treated with SGLT2i. Further studies are warranted to evaluate the effect of SGLT2i therapy on outcome in patients undergoing LLA. Graphical abstract