Metformin Improves Outcome in Digit Amputation

Introduction: Metformin is often used for diabetic patients. It, in general, is also classified as senomorphic. This means it blocks senescent cells from secreting the SASP factors (Senescence-associated secretory phenotype), which are a combination of secretory molecules such as pro-inflammatory cytokines, chemokines, proteases, bioactive lipids, inhibitory molecules, and other factors, promoting a state of chronic inflammation and tissue dysfunction. Chronic wounds are a common comorbidity associated with type II diabetes and metabolic dysfunction. There are over 12 million Americans suffer from chronic, non-healing wounds, presenting a serious health care and socioeconomic burden annually. Digit amputations are common in Diabetic foot ulcers that fail conservative treatment. We hypothesized that patients using Metformin have better outcomes than those not using it when having digit amputation.Methods:We reviewed retrospectively 259 patients who had digit amputation from 2013 to 2017. The Institutional Review Board approved an exemption for this review. Forty-six patients used Metformin (group A). We matched with 46 patients not taking Metformin for age, gender, and year of surgery (group B). We compared the two groups' healing time and the need for more proximal amputations. An association correlation between proximal amputations and the use of Metformin was analyzed using Fisher’s Exact test.Results:In group A, 37 (80.4%) healed the digit amputation in 45 ± 26 days of patients who took Metformin. In group B, 28 (60.9%) of patients not taking Metformin healed in 47 ± 47 days. Group A had six (13%) midfoot amputations, and group B had nine (19.6%) (p = 0.1575). Group A had three (6.5%) major amputations, and group B had nine (19.6%) (p = 0.0461).   Discussion: Metformin appears to improve healing in digit amputation. This study only reviewed surgical outcomes; a review with a larger number of participants using senolytic drugs versus other diabetic drugs will strengthen the effect of Metformin.References:1. Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536. doi: 10.1111/joim.13141. Epub 2020 Aug 4. 2. Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA; IWGDF Editorial Board. Practical Guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3266. doi: 10.1002/dmrr.3266. 3. Yammine K, Hayek F, Assi C. A meta-analysis of mortality after minor amputation among patients with diabetes and/or peripheral vascular disease. J Vasc Surg. 2020 Dec;72(6):2197-2207. doi: 10.1016/j.jvs.2020.07.086. Epub 2020 Aug 21.