Front Endocrinol (Lausanne). 2026 Sep 16;17:1922755. doi: 10.3389/fendo.2026.1922755. eCollection 2026.
ABSTRACT
BACKGROUND: Diabetic foot infection (DFI) is a major cause of non-traumatic lower-limb amputation and is associated with poor survival outcomes. Identifying therapies that reduce progression to amputation is critical.
OBJECTIVE: To evaluate the association between statin therapy and risk of amputation in patients with DFI, including assessment of dose-response effects.
METHODS: A retrospective cohort study involving 376 patients presenting with DFI at a university hospital in Jordan between January 2020 and April 2024. The primary outcome was amputation severity (no amputation, minor amputation, major amputation), analyzed using multivariable ordinal logistic regression, adjusting for potential confounders; major amputation incidence was also examined as a secondary binary outcome for absolute risk reduction and number-needed-to-treat calculations.
RESULTS: Moderate-intensity statin therapy was associated with an absolute risk reduction (ARR) of 9.3% (NNT = 11) for major amputation, while high-intensity therapy was associated with an ARR of 14.3% (NNT = 7). In adjusted ordinal logistic regression models, both moderate-intensity (aOR 0.43, 95% CI 0.20-0.74, p = 0.004) and high-intensity statins (aOR 0.43, 95% CI 0.26-0.71, p = 0.001) were associated with lower odds of more severe amputation. A significant dose-response trend was observed, with major amputation rates decreasing from 21.9% in untreated patients to 12.6% and 7.6% in moderate- and high-intensity groups, respectively (p = 0.025). Subgroup analyses showed consistent associations across key clinical subgroups, including patients with advanced Wagner grades, peripheral arterial disease, and neuropathy.
CONCLUSION: Statin therapy was associated with lower odds of more severe amputation and a lower observed risk of major amputation in patients with diabetic foot infection. An ordered trend in risk reduction was observed across statin intensity levels, but moderate- and high-intensity statins did not differ significantly from one another, so these findings support an association with statin use rather than a confirmed dose-dependent gradient. Further randomized controlled trials are needed to confirm causality and evaluate long-term outcomes.
PMID:42818660 | PMC:PMC13623674 | DOI:10.3389/fendo.2026.1922755