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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1424544
This article is part of the Research Topic Diabetes and cardiovascular disease: new therapeutic interventions View all 10 articles

Autonomic Modulation by SGLT2i or DPP4i in Patients with Diabetes Favors Cardiovascular Outcomes as Revealed by Skin Sympathetic Nerve Activity

Provisionally accepted
Jien-Jiun Chen Jien-Jiun Chen 1*Chen Lin Chen Lin 2Men-Tzung Lo Men-Tzung Lo 2Lian-Yu Lin Lian-Yu Lin 3Hsiang-Chih Chang Hsiang-Chih Chang 2Geng-Chi Liu Geng-Chi Liu 2
  • 1 National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
  • 2 National Central University, Jungli City, Taoyuan County, Taiwan
  • 3 National Taiwan University Hospital, Taipei, Taiwan

The final, formatted version of the article will be published soon.

    Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuroelectrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Methods Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs. 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs. 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4itreated group (0.084 ± 0.028 vs. 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS.We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function.

    Keywords: NeuECG, skin sympathetic nerve activity, autonomic modulation, Entropy analysis, Sodium-glucose cotransporter 2 inhibitor

    Received: 28 Apr 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Chen, Lin, Lo, Lin, Chang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jien-Jiun Chen, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan

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