The evidence gap inside "metabolic peptides"
Marketing puts semaglutide and growth-hormone secretagogues in the same "metabolic peptide" bucket. The evidence does not. Incretin-based drugs have been tested in tens of thousands of participants in randomised trials with hard outcomes — HbA1c, body weight, cardiovascular events. Growth-hormone secretagogues have been tested in dozens to a few hundred participants, mostly for hormone levels rather than clinical outcomes.
What is established
- Semaglutide and tirzepatide reduce body weight and improve glycaemic control in randomised placebo-controlled trials lasting more than a year, and both carry FDA approvals for these uses. Semaglutide has also shown reduction in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity (SELECT trial).
- Tesamorelin reduces visceral adipose tissue in people with HIV-associated lipodystrophy and is FDA-approved for that narrow indication.
What is not
- CJC-1295 and ipamorelin raise growth hormone and IGF-1 in short human pharmacology studies. Whether that changes body composition, insulin sensitivity or anything a patient would notice has not been shown in controlled trials.
- Claims that GH secretagogues are a "natural" or "safer" alternative to GLP-1 drugs are not evidence-based; the two classes have not been compared, and secretagogues lack the long-term safety data the incretin drugs have accumulated.
Open questions we are tracking
- Durability of weight loss after stopping GLP-1/GIP therapy (STEP 1 extension and SURMOUNT-4 data show substantial regain).
- Lean-mass loss during rapid weight reduction and whether resistance training or protein intake mitigates it.
- Compounded and counterfeit semaglutide/tirzepatide safety, which the FDA has issued warnings about.