Discussion
hyperglycemia, hypoglycemic, Hypoglycemia, diabetes
HYPERGLYCEMIA, DIABETES, BLIND, EVENTS, TYPE 2 DIABETES, HYPOGLYCEMIA
This was a phase 3, prospective, double blind, randomized, placebo-controlled, multi-center, pivotal study to investigate the efficacy and safety of TENS in improvement of glycemic control in patients with type 2 diabetes. The primary efficacy endpoint is to compare the HbAHowever, according to the subgroup analysis, we found that female patients in the TENS group but not the placebo group exhibited a significant HbAWe further found that the 7-point SMBG maintained a relatively more stable GV in the TENS group compared to the placebo group, as reflected by MAGE reduction, with a greater decline found throughout the study in the TENS group compared to the placebo group. From week 0 to week 20, MAGE decreased 19 mg/dL in the TENS group and 9 mg/dL in the placebo group and became significantly different at week 20 (Fig. The significant effect of TENS on MAGE reduction is a post-hoc novel finding of our study. MAGE has long been recognized as an indicator of GV and thus represented as an important part of diabetes control because of the need to reach target HbARegarding the safety aspect of the study device, over 80% of TEAEs were mild, and no serious adverse device effects were reported. Hypoglycemia was the most common AE presented with six events occurring in five subjects receiving TENS and 14 events occurring in nine subjects receiving placebo, while hyperglycemia requiring rescue medication was encountered in one subject in the TENS group vs. three subjects in placebo group. Overall, patients in the TENS group experienced less hypoglycemic and hyperglycemic events when compared to placebo, which corroborates with the previous finding that TENS is associated with significant reduction in GV. We propose the underlying mechanism might involve the harmonious regulation of glucagon and insulin secretions associated with TENS, leading to maintenance of optimal glucose homeostasisThroughout the study, we also found significant decline of CRP from baseline in the TENS group, but not in the placebo group. In addition, CRP and FGF-21 showed significant group effects in the TENS group vs. the placebo group. Although the other biomarkers examined in this study did not show significant change, the decreases in CRP and FGF-21 in the TENS group demonstrated potential improvement in systemic inflammationThe limitations of this study are listed as below. First, the duration of the study was only 20 weeks, and it is not known whether the MAGE reduction would be sustained or even better for a longer duration as revealed in this study in a time-dependent manner. An extension of the study period to 40 weeks might help to answer the question. Second, since continuous glucose monitoring (CGM)-derived MAGE has been shown to be more accurate than that derived from self-monitoring of blood glucoseIn conclusion, the domestic use of both “Dragon Waves Resonant Home Care” Transcutaneous Electronic Nerve Stimulator (TENS) and placebo (sham TENS ineffective pulse wave) demonstrated a modest effect in glycemic control and were well tolerated without safety concerns in patients with type 2 diabetes. Nonetheless, for the primary endpoint, TENS did not demonstrate a statistically difference in the HbA