Recombinant hormone

Intranasal insulin is ordinary human insulin sprayed high into the nose so that some of it travels into the brain, where insulin receptors are dense in memory regions, while blood insulin and glucose barely change. Small trials found better memory in healthy adults and in people with mild cognitive impairment or Alzheimer's, but the largest trial, a 12-month phase 2/3 study in 289 people, found no benefit. Several trials in older surgical patients reported less delirium after surgery.

Somatropin is recombinant human growth hormone — the 191-amino-acid protein itself, which is what "HGH 191AA" on a vial means. It is a long-approved prescription medicine for growth hormone deficiency and several causes of short stature. Outside those uses, the evidence is much less flattering than its reputation. In healthy older adults, a meta-analysis of 18 study populations found about 2.1 kg more lean mass and 2.1 kg less fat, no weight change, no improvement in bone density, and significantly more soft-tissue swelling, joint pain, carpal tunnel syndrome, gynecomastia and new diabetes — concluding it cannot be recommended as an anti-aging therapy. In young athletes the pattern repeats: lean mass up 2.1 kg, strength and exercise capacity not improved, and more swelling and fatigue.

Teriparatide is the first 34 amino acids of human parathyroid hormone, and it is the odd one out in this group: a licensed medicine with a fracture-outcome trial behind it. Parathyroid hormone continuously elevated - as in hyperparathyroidism - destroys bone. Given as a single daily injection it does the opposite and builds it, which is one of the more surprising dose-schedule effects in pharmacology. The pivotal trial randomized 1637 postmenopausal women with prior vertebral fractures: new vertebral fractures occurred in 14% on placebo against 5% and 4% on 20 µg and 40 µg. VERO later compared it head to head with risedronate in severe osteoporosis and found new vertebral fractures in 5.4% against 12.0%, a hazard ratio of 0.44. It is included here because it is a peptide bioregulator in the literal sense - and because it shows what the rest of this group's evidence would look like if it existed.