Comparing the four biological responses
There is a useful comparison here. It starts by naming what each experiment was trying to change.
Different targets and endpoints
I cannot nominate a best peptide across growth-hormone release, sexual desire and weight management. The conditions and outcomes are too different for that contest. Comparing the actual questions is more revealing.
| Compound | Biological target | What the cited human study measured |
|---|---|---|
| Ipamorelin | Ghrelin receptor, GHS-R1a | Time to a tolerated meal after bowel resection; primary endpoint missed |
| PT-141 | Melanocortin receptors, chiefly MC4R | Desire and desire-related distress in premenopausal women with HSDD; significant improvements |
| Semaglutide | GLP-1 receptor | Body-weight change in adults with overweight or obesity without diabetes, plus separate cardiovascular and kidney outcomes |
| Tirzepatide | GIP and GLP-1 receptors | Body-weight change versus semaglutide in adults with obesity without type 2 diabetes; greater reduction with tirzepatide |
The shared peptide chemistry makes these molecules relatives in one sense. Their clinical questions send them in different directions.
Desire, reward and reported hunger
A desire questionnaire, a hamster reward experiment and a description of intrusive food thoughts belong to different levels of experience. PT-141's human imaging study and hamster experiment are particularly useful together because the distinction is so easy to flatten. They concern different species and different outcomes.
Reports of altered wanting draw me in, whether sexual or food-related. Community accounts of quieter food thoughts, better sleep or stronger sexual interest remain anecdotal and unverified. They offer questions for research, with no basis for assuming a single shared mechanism across all four peptides.
SURMOUNT-5 in context
Semaglutide and tirzepatide do share a direct weight comparison. In SURMOUNT-5, mean body-weight change at 72 weeks was -20.2% with tirzepatide versus -13.7% with semaglutide, using maximum tolerated doses in 751 adults with obesity without type 2 diabetes. The trial was open-label. That finding establishes the direction of the weight result under those conditions.
The separate organ-outcome studies deserve space beside the weight comparison. Semaglutide's SELECT cardiovascular trial and FLOW kidney trial address outcomes that cannot be ranked by a weight-loss percentage. Those studies give semaglutide a clinical story that survives a less favourable weight comparison.
Approval and preparation
Ipamorelin has no FDA approval. PT-141's approved bremelanotide formulation covers acquired, generalized HSDD in premenopausal women. Approved semaglutide formulations cover diabetes, weight management, cardiovascular risk reduction and MASH; approved tirzepatide formulations cover diabetes, weight management and moderate-to-severe obstructive sleep apnea in adults with obesity. A compounded preparation has no FDA approval.
On FDA's page current as of April 22, 2026, ipamorelin acetate's withdrawn 503A nomination retains safety concerns, while it remains Category 2 under the separate 503B policy. Neither listing authorizes compounding. The questions page supplies the safety context alongside the results.