2019;31(10):e12787
Tirzepatide, for example, is a dual GLP-1/GIP receptor agonist that was recently approved for treatment of type 2 diabetes
189 Subsequently, tirzepatide has been extensively investigated in the SURPASS program, a comprehensive development initiative targeting T2DM that is inadequately controlled by various glucose-lowering regimens, including lifestyle alone (SURPASS-1), 190 metformin monotherapy (SURPASS-2), 191 metformin with or without sodium-glucose co-transporter 2 inhibitors (SGLT2i) (SURPASS-3), 192 combination therapy including metformin, SGLT2i, and sulfonylureas (SURPASS-4), 193 insulin glargine with or without metformin (SURPASS-5), 88 and insulin lispro with basal insulin (SURPASS-6)
Moreover, the improvement deepened over the first year of dosing (4,5)
Another glutaminase inhibitor, JHU-083, extensively inhibits Gln-metabolizing enzymes and increases the concentrations of Gln and glucose in the TME by inhibiting glycolysis, relieving the hypoxic state
Technically, it conjugates to toxins using the enzyme glutathione-S-transferase (GST) to allow them to be eliminated in the urine
