To compare the contribution of sodium-glucose cotransporter-2 inhibitors (SGLT2is) with that of DPP4i or GLP-1ra toward lower extremity amputation rate.Electronic databases were searched for articles published on the differences between the rates of lower extremity amputation among patients with type 2 diabetes mellitus (T2DM) undergoing SGLT2i treatment and those undergoing other anti-hyperglycemic agent (dipeptidyl peptidase-4 inhibitors [DPP4is], glucagon-like peptide-1 receptor agonist [GLP-1as], or sulfonylurea [SUs]) treatments. Random-effect models were used to generate data if heterogeneity was detected.Eight studies based on retrospective case-control designs with propensity matching were included. The propensity score-matching method increased credibility. Compared with SGLT2i treatment, DPP4i or GLP-1a treatment tended to result in a higher amputation rate (pooled hazard ratio [HR] = 1.1, 95% confidence interval [CI]: 0.98-1.23), whereas SU treatment resulted in similar amputation rates (pooled HR = 0.92, 95% CI: 0.74-1.13). After excluding the heterogeneous study, the meta-analysis of the remaining studies attained a statistical value (pooled HR = 0.81, 95% CI: 0.65-1.01).The study findings suggest that, with respect to diabetic foot-related limb amputations, SGLT2is are not superior to novel anti-hyperglycemic agents (DPP4is and GLP-1as) or other types of oral hypoglycemic agents (SUs). Therefore, SGLT2is may not have significantly positive effects on the prognosis for T2DM patients with complicated diabetic foot.Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.