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In the SURPASS-2 study, the three doses of tirzepatide (5, 10, and 15 mg once weekly) were tested with the GLP-1RA semaglutide (1 mg once weekly) as a comparator in patients not optimally controlled on monotherapy with metformin (71)
They boost insulin secretion during meals, which can lower blood glucose spikes after eating
Vrang and Grove, 2011
Their cognate receptors, GIPR, GLP-1R and GCGR, belong to class B1 G protein-coupled receptor (GPCR) family
Glucagon typically raises blood glucose, but in the context of GLP-1 receptor coactivation (which suppresses glucagon's glucose-raising effect), the net result appears to be enhanced fat mobilization and thermogenesis without significant glycemic risk
Orforglipron won on both endpoints: A1C dropped 2.2% versus 1.4% with oral semaglutide, and weight loss was 9.2% versus 5.3%
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