Gabriel, Rafael (7103316027)Rafael (7103316027)GabrielBoukichou-Abdelkader, Nisa (57216392995)Nisa (57216392995)Boukichou-AbdelkaderGilis-Januszewska, Aleksandra (7801318789)Aleksandra (7801318789)Gilis-JanuszewskaMakrilakis, Konstantinos (6603246389)Konstantinos (6603246389)MakrilakisGómez-Huelgas, Ricardo (7004734060)Ricardo (7004734060)Gómez-HuelgasKamenov, Zdravko (6603678114)Zdravko (6603678114)KamenovPaulweber, Bernhard (36519500600)Bernhard (36519500600)PaulweberSatman, Ilhan (6603732754)Ilhan (6603732754)SatmanDjordjevic, Predrag (57200124383)Predrag (57200124383)DjordjevicAlkandari, Abdullah (56182455000)Abdullah (56182455000)AlkandariMitrakou, Asimina (7004179428)Asimina (7004179428)MitrakouLalic, Nebojsa (13702597500)Nebojsa (13702597500)LalicEgido, Jesús (35463099300)Jesús (35463099300)EgidoMás-Fontao, Sebastián (6701721229)Sebastián (6701721229)Más-FontaoCalvet, Jean Henri (37664688100)Jean Henri (37664688100)CalvetPastor, José Carlos (56871286300)José Carlos (56871286300)PastorLindström, Jaana (55646081100)Jaana (55646081100)LindströmLind, Marcus (13402929500)Marcus (13402929500)LindAcosta, Tania (36518089000)Tania (36518089000)AcostaSilva, Luis (57216391876)Luis (57216391876)SilvaTuomilehto, Jaakko (36012823000)Jaakko (36012823000)Tuomilehto2025-06-122025-06-122023https://doi.org/10.3390/jcm12052035https://www.scopus.com/inward/record.uri?eid=2-s2.0-85150221425&doi=10.3390%2fjcm12052035&partnerID=40&md5=c8b12308c42ab58d103e4cc1392f7cd4https://remedy.med.bg.ac.rs/handle/123456789/2758Objective: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. Methods: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR). Results: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3–33.9) with metformin alone, by 17.3% (95% CI 7.4–27.2) with linagliptin alone, and by 19.5% (95% CI 10.1–29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38–6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy −0.3 mmol/L (95%CI: −0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin −0.2 mmol/L (95% CI: −0.37; −0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by −2.0 kg (95% CI: −5.65; −1.65, p = 0.0006) with metformin monotherapy, and by −1.9 kg (95% CI: −3.02; −0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). Conclusions: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo. © 2023 by the authors.antidiabetic drugsglomerular filtrationlifestyle interventionperipheral neuropathy riskprediabetes