Importantly, the effects of RAMPs are agonist- and pathway-dependent, with RAMP2 increasing Gαs coupling at GCGR in response to glucagon and oxyntomodulin (an endogenous dual agonist of both GCGR and GLP-1R) but decreasing the response to GLP-1 and liraglutide (a synthetic, lipidated GLP-1 mimetic, approved in the treatment of T2DM) (13). This evidence concerns the gene GCG and type 2 diabetes mellitus.