Evaluating the Impact of Diabetes and Metformin on Painful Neuromas After Lower Extremity Amputations

Abstract

Background: Painful neuromas are common cause of residual limb pain following lower extremity amputation, yet its incidence in diabetic populations remains unestablished. While diabetes is thought to reduce neuroma risk due to impaired nerve regeneration, the role of metformin on this process remains unclear. This study aims to explore the association of diabetes severity and metformin therapy on painful neuroma formation following lower extremity amputations.

Methods: This retrospective cohort study used TriNetX Research Network to identify adult patients (≥18 years) who underwent lower extremity amputation between January 2016 to February 2024. Patient cohorts were identified using International Classification of Disease-10 and Current Procedural Terminology codes. Patients were stratified by diabetic status, hemoglobin A1c levels, and metformin use. Propensity score matching was performed and adjusted for demographics, comorbidities, and medications. Risk differences, risk ratios, and odds ratios with corresponding 95% confidence intervals were calculated to quantify the association between the exposure and the outcome. Statistical significance was set at P < 0.05.

Results: A total of 16,090 patients underwent lower extremity amputation, 9994 (62.1%) were diabetic, while 6096 (37.9%) were nondiabetic. The overall incidence of symptomatic neuromas was lower in diabetic patients (0.61%) compared to the nondiabetic group (1.67%). After propensity score matching, 5196 diabetic and 5104 nondiabetic amputees were identified. Diabetes was associated with a significant reduction in neuroma risk [risk difference of -0.893% (95% CI: -1.29% to -0.496%); P < 0.0001]. Patients using metformin at the time of surgery had a higher incidence of painful neuroma (0.718%) compared to nonusers (0.424%) ( P = 0.127, odds ratio = 1.69). There was no significant difference in neuroma rates between those with hemoglobin A1c levels 6.5%-8.0%, 8.1%-10%, and >10%.

Conclusions: Diabetes was associated with a lower painful neuroma risk after amputation, suggesting a possible protective role of hyperglycemia-induced nerve regeneration alterations. Metformin use had no significant impact on painful neuroma rates. These findings challenge assumptions about glycemic control and neuroma formation, highlighting the need for further research on metabolic influences in postamputation nerve healing and pain management.

Keywords: diabetes; lower extremity amputation; metformin; neuroma.