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This risk appears not to be due to differences in baseline characteristics between the cohorts. Joseph F

The major methyltransferases are: COMT (catechol-O-methyltransferase) : inactivates catecholamines (dopamine, norepinephrine, epinephrine), catechol estrogens, and catechol drugs (L-DOPA) R HNMT (histamine N-methyltransferase) : the primary intracellular histamine degradation enzyme in the brain and peripheral tissues R INMT (indolethylamine N-methyltransferase) : methylates tryptamine, serotonin, and other indoleamines R NNMT (nicotinamide N-methyltransferase) : methylates nicotinamide (vitamin B3) and other pyridines R TMT (thiol S-methyltransferase) : S-methylates thiol drugs (captopril, D-penicillamine) and thiol metabolites R TPMT (thiopurine S-methyltransferase) : methylates thiopurine drugs (azathioprine, 6-mercaptopurine) used in autoimmune disease and cancer R Methylation capacity depends on the methylation cycle: methionine to SAM-e to SAH to homocysteine, recycled back to methionine by methionine synthase (B12-dependent) or BHMT (betaine-dependent)

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Phase 2 tirzepatide dose-ranging in T2D 1, 5, 10, and 15 mg over 26 weeks