Journal Article

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial

Pastor, José Carlos, Paulweber, Bernhard, Boukichou-Abdelkader, Nisa, Makrilakis, Konstantinos, Calvet, Jean Henri, Lind, Marcus, Lalic, Nebojsa, Kamenov, Zdravko, Satman, Ilhan, Lindström, Jaana, Más-Fontao, Sebastián, Silva, Luis, Gómez-Huelgas, Ricardo, Djordjevic, Predrag, Gabriel, Rafael, Mitrakou, Asimina, Egido, Jesús, Tuomilehto, Jaakko, Alkandari, Abdullah, Gilis-Januszewska, Aleksandra, Acosta, Tania

2023

Overview

Objective: 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.

• Publisher: MDPI AG,MDPI
• Subject: Analysis / antidiabetic drugs / Antidiabetics / Care and treatment / Clinical Medicine / Clinical trials / Development and progression / Diabetes / Diabetic retinopathy / Dosage and administration / Drug dosages / Drug therapy / Drug therapy, Combination / glomerular filtration / Glucose / Hyperglycemia / Hypoglycemic agents / Intervention / Kidney function tests / Klinisk medicin / lifestyle intervention / Lifestyles / Patient outcomes / Peripheral neuropathy / peripheral neuropathy risk / prediabetes / Prediabetic state / Prevention / Type 2 diabetes