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GLP-1 activation primarily causes nausea and appetite suppression, while GIP signaling contributes to energy metabolism changes

However, GIP receptor (GIPR) activity is diminished in patients with type 2 diabetes (T2D), while GLP-1 receptor (GLP-1R) function remains intact (4)

Metformin acts mainly by inducing liver and skeletal muscle serine/threonine kinase B1 (LKB1), which activates AMP-activated protein kinase (AMPK) by phosphorylating Thr 172 of the AMPK chain [2]

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