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Metformin, the current first-line treatment in T2DM, has an unclear antidepressant effect [166] despite identified direct mechanisms and pleiotropic effects, including inhibition of angiotensin II and NF-B factor, normalization of gut microbiota, and intestinal permeabilization, and in vivo experimental data [167] supporting its potential benefits

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Glucagon-like peptide-1 reduces pancreatic -cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats

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Notably, liraglutide and semaglutide are also globally approved for treating obesity [175]