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It was first discovered in the early 1970's, where Loren Pickart found out that the complex positively affected older liver cells, making them function like liver cells of much younger individuals

Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist, for People with Type 2 Diabetes: A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial. The New England Journal of Medicine

Haugaard SB, Andersen O, Hansen BR, Orskov H, Andersen UB, Madsbad S, Iversen J, Flyvbjerg A: Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

Wang Q, Zhang Q, Luan S, et al

Raised, rolled, reddened, or darkened wound edges might reflect delayed healing or pathological changes, while dryness, flaking, redness, tension, shininess, or pigmentation changes in adjacent skin can signal abnormal tissue responses [27]

Tier 3 also includes medications that have some evidence in the elderly but that have not been adopted for use in most practices