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Multicenter trials would provide sufficient power to detect clinically meaningful effects and assess safety across diverse patient populations
Small PBMs or new entrants find it difficult to compete unless they offer radically different models (e.g., transparent pass-through PBMs, or tech-focused startups)
Having side effects that are limiting your food and fluid intake
Association of glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: a meta-analysis of randomized controlled trials
This approach inspired other programmes: N-hexanoic-Tyr-D-Arg : enkephalin-derived, protease-resistant, studied for pain N-methyl-Aib inclusions : N-methyl substitutions increase membrane permeability at the cost of partial loss of receptor affinity Beta-peptides and D-amino acids : substitution of natural chiral residues by their D enantiomers, making the peptide invisible to endogenous proteases while (sometimes) preserving function Stapled peptides : hydrocarbon cyclisation, popularised by Verdine (Harvard), stabilises alpha helices and improves cellular penetration These strategies progressively shift the peptide / small molecule frontier
Georgakis GV, Li Y, Humphreys R, Johnson R, Andreeff M , Fiscella M, Pukac L, OBrien S, Albert V, Younes A
