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Participants also recorded reductions in waist circumference (average 7.1cm loss on 6mg, 8.2cm on 12mg, 10cm on 36mg, compared with 3.1cm loss on placebo), blood pressure (estimated -4.2 and -1mm HG difference between placebo and orforglipron in systolic and diatolic blood pressure, respectively) and cholesterol (-2.1% difference between placebo and orforglipron)

This reinforces the need for carefully titrated regimens, especially in clinical settings where circadian timing (chronopharmacology) may dictate efficacy

Gut microbiota dysbiosis can disrupt the components of the GBA, leading to mood, cognition, and behaviour alterations [113]

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Oxidative metabolism signatures predict response to 5FU-based chemotherapy treatment Given this robust adaptation to facilitate cellular survival in cancer cells treated with 5FU, we next postulated that elevated mitochondrial metabolism may be a predictor of response to 5FU-based chemotherapy