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SGLT2is decrease plasma glucose levels through inhibition of renal glucose reabsorption in the proximal tubule, which results in increased glucose excretion by the kidneys

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Antagonising glucagon receptors (GCGRs) with modified glucagon analogues, small molecules or antisense oligonucleotides has also been problematic because of the risk of hypoglycaemia and adverse effects on liver function, including steatosis and an increase in LDL-cholesterol

Measurement of zonulin levels in serum or gut tissue can assess the start of permeability-regulating pathways

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