Gabriel Rafael, Boukichou-Abdelkader Nisa, Gilis-Januszewska Aleksandra, Makrilakis Konstantinos, Gómez-Huelgas Ricardo, Kamenov Zdravko, Paulweber Bernhard, Satman Ilhan, Djordjevic Predrag, Alkandari Abdullah, Mitrakou Asimina, Lalic Nebojsa, Egido Jesús, Más-Fontao Sebastián, Calvet Jean Henri, Pastor José Carlos, Lindström Jaana, Lind Marcus, Acosta Tania, Silva Luis, Tuomilehto Jaakko
Departamento de Salud Internacional, Escuela Nacional de Sanidad, Instituto de Salud Carlos III, 28029 Madrid, Spain.
World Community for Prevention of Diabetes Foundation (WCPD), 28001 Madrid, Spain.
J Clin Med. 2023 Mar 3;12(5):2035. doi: 10.3390/jcm12052035.
To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes.
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).
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 ( < 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 ( = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo ( = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, = 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 ( = 0.0002).
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.
比较降糖药物对糖尿病前期患者周围神经和肾功能的影响。
对658例糖尿病前期成年人进行多中心、随机、安慰剂对照试验，患者接受二甲双胍、利格列汀、二者联合治疗或安慰剂治疗1年。观察终点为通过足部电化学皮肤电导（FESC<70微西门子）评估的小纤维周围神经病变（SFPN）风险和估计肾小球滤过率（eGFR）。
与安慰剂相比，单独使用二甲双胍时SFPN比例降低25.1%（95%CI：16.3 - 33.9），单独使用利格列汀时降低17.3%（95%CI 7.4 - 27.2），利格列汀/二甲双胍联合使用时降低19.5%（95%CI 10.1 - 29.0）（所有比较P<0.0001）。利格列汀/二甲双胍联合使用时eGFR比安慰剂组高+3.3 mL/分钟（95%CI：0.38 - 6.22）（P = 0.03）。空腹血糖（FPG）在二甲双胍单药治疗时降低更多，为-0.3 mmol/L（95%CI：-0.48；0.12，P = 0.0009），二甲双胍/利格列汀联合治疗时降低-0.2 mmol/L（95%CI：-0.37；-0.03），均优于安慰剂组（P = 0.0219）。与安慰剂相比，二甲双胍单药治疗时体重（BW）降低-2.0 kg（95%CI：-5.65；-1.65，P = 0.0006），二甲双胍/利格列汀联合治疗时降低-1.9 kg（95%CI：-3.02；-0.97）（P = 0.0002）。
在糖尿病前期患者中，与安慰剂治疗相比，二甲双胍和利格列汀联合或单药治疗1年与较低的SFPN风险相关，且eGFR降低幅度较小。
