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Insulin resistance plays an important role in the pathophysiology of comorbid T2DM and depression and can be a trigger for dysregulation of insulin- and GLP-1-mediated signaling (both central and peripheral), neuroendocrine disorders (hypothalamicpituitaryadrenal system dysfunction and monoaminergic neurotransmission disorders), chronic low-intensity inflammation, oxidative stress, and disorders of the microbiota-gut-brain system, reducing the level of neurotrophic factors in the brain and changing synaptic plasticity

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As tirzepatide clears over 3-4 weeks, gastrointestinal symptoms typically improve gradually, appetite may return, and blood glucose levels may rise in patients with diabetes