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Rybelsus has now demonstrated proven cardiovascular risk reduction in the landmark SOUL trial (McGuire et al., NEJM 2025)
Discussion Building on previous human and animal studies, the authors propose a number of possible mechanisms responsible for their findings, including that the beneficial effects of earlier metformin administration may reflect the time taken for metformin to influence glucose transporters in the upper small intestine, reducing glucose absorption, and that this may link to increased GLP-1 secretion
The two principal combinations are BPC-157 plus TB-500 (mechanistically distinct, pentadecapeptide signalling plus actin sequestration), and BPC-157 plus TB-500 plus GHK-CU (three-compound research design covering pentadecapeptide, thymosin family, and copper tripeptide pathways)
The combination approach of targeting two separate pathways produces results competitive with even the most effective single-agent therapies currently available
Cai S, Xie LW, Xu JY, Zhou H, Yang C, Tang LF, Tian Y, Li M
