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We and others previously demonstrated GDF8 and ActA are the two major ligands which mediate the muscle minimization actions of the ActRIIA/B receptors in non-obese mice and NHPs 22,28,30 , and we have further shown that dual blockade of GDF8 and ActA led to much larger increases in muscle mass than blocking either ligand individually, and that dual blockade matched the muscle growth actions of broader ActRIIA/B blockade 28 , similar to effects seen when using a dominant-negative type II receptor or pro-domains of GDF8 and activins 22,26,27

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Given existing evidence, triple combination therapy can be expected to provide additional cardiorenal protection, although further randomized controlled trials are needed to determine whether triple combination therapy actually has additive or synergetic effects compared with mono or dual therapy

12 , 18 , 21 , 24 It is also important to acknowledge that the influence of other unrecognized or under-reported GI motility disorders may have been underestimated in the included populations