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The neuronal dysfunction that characterizes diabetes,16 hyperglycemia, and dietary modifications that include the use of sweeteners, as well as a greater predisposition to certain psychologic disorders,16 are some of the factors that can independently contribute to or interact together for the development and progression of gastrointestinal symptoms in this group of patients with psychologic disorders.16,17 Diabetic gastrointestinal neuropathy Diabetic gastrointestinal neuropathy can affect any part of the gastrointestinal tract, manifesting as gastroparesis, constipation, or fecal incontinence secondary to visceral neuropathy.16,18 Chronic hyperglycemia conditions an altered enteric microenvironment, with increased oxidative stress, the formation of advanced glycosylation end products, inflammation, and reduced neurotransmitters and local hormones, affecting the enteric vasculature and smooth muscle cellularity.19 Previously described changes affect the sensory, motor, and secretory functions of the digestive tract, contributing to the wide range of gastrointestinal alterations mentioned.18 Gastroparesis is one of the most widely studied gastrointestinal manifestations of diabetic gastrointestinal neuropathy

3.3 Tirzepatide effects: cardiovascular, renal, hepatic, and other metabolic effects of tirzepatide Due to concerns that type 2 diabetes medications increased cardiovascular risk, the FDA issued guidance for pharmaceutical companies to perform cardiovascular outcomes trials for new diabetes medications

Fructose significantly increases GIP secretion in streptozotocin-treated, hyperglycemic mice in a K ATP -dependent manner (Seino et al., 2015) and in ob/ob mice ( ATP channel activation (diazoxide) (Ogata et al., 2014)

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Terns Pharmaceuticals (TERN-601) has an oral GLP-1 agonist in Phase 1/2