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These rates appear to be higher than those reported in clinical trials, for example, 22.6% of patients prematurely discontinued therapy during the 24-month trial period in the SUSTAIN 6 trial of semaglutide [37], and 27.6% of randomised patients prematurely discontinued albiglutide during the 25-month trial period in the HARMONY trial [86]
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The molecular mechanism underlying lactate-induced downregulation of ACSL4 via MCT1 remains incompletely elucidated, although accumulating evidence suggests a potential involvement of the lactate-induced STAT3 signaling pathway (197,198)
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