Peptides honestly — three tiers.

There are three tiers of peptide in the actual world. They have very different risk profiles. The supplement industry, the wellness clinic industry, and the influencer industry blur the lines.

Tier 1: FDA-approved drugs

These are real medicines that happen to be peptides. They've been through Phase 3 trials, the FDA has approved them for specific indications, and they're prescribed legitimately by physicians.

Semaglutide (Ozempic, Wegovy, Rybelsus). GLP-1 agonist. Approved for type 2 diabetes (Ozempic/Rybelsus) and chronic weight management (Wegovy). The STEP-1 trial, 2021 NEJM showed 14.9% weight loss vs 2.4% placebo at 68 weeks. Largest weight-loss effect ever shown by a pharmacological intervention.

Tirzepatide (Mounjaro, Zepbound). Dual GLP-1/GIP agonist. Approved 2022 for diabetes, 2023 for weight management. SURMOUNT-1, 2022 NEJM: 20.9% weight loss at highest dose vs 3.1% placebo at 72 weeks. Stronger than semaglutide.

Liraglutide (Saxenda). Earlier GLP-1, daily injection, less effective than semaglutide. Still approved, less commonly used now.

For midlife women specifically, the weight-loss applications are increasingly being prescribed alongside HRT — and the early signal is that the combination works particularly well for the post-menopausal visceral fat redistribution problem we discussed in letter #2.

Side effects are real: nausea (40-50% in first month, usually fades), constipation, gallstones at higher doses, muscle loss if protein intake is inadequate. The muscle-loss issue is why these drugs need to be paired with resistance training and 0.8g+ protein/lb. Without that, you lose weight but lose disproportionate lean mass.

Tier 2: Telehealth-prescribed compounded peptides

This is the wellness-clinic category. Companies like Hims, Henry Meds, MOCHI Health, and many local "peptide clinics" prescribe compounded versions of FDA-approved drugs — usually because the brand-name versions are too expensive or out of stock.

Compounded semaglutide and tirzepatide are legal under FDA shortage rules. Quality varies enormously. Some compounders are scrupulous; some are not. The 2024 FDA warnings on compounded semaglutide are worth reading before going this route.

Compounded NAD+ peptides, MOTS-c, peptide stacks — many of these have weak or no human evidence. The clinic is selling you something with "research suggests" claims but no FDA approval and no Phase 3 data.

If you go telehealth, ask: who is the compounding pharmacy, what is their 503A/503B status, what testing do they do on each batch?

Tier 3: Research-grey peptides

BPC-157, TB-500, CJC-1295, Ipamorelin, Epitalon — these have promising animal data and small human studies but no FDA approval for any indication. They're sold as "research compounds not for human use" — and then a parallel industry sells them for human use anyway.

This is the category we will not write a buying guide for. Not because the molecules are necessarily dangerous (some have decent safety signals), but because the supply chain is unregulated, the purity is unknown, and the dosing recommendations come from internet protocols rather than clinical trials.

If you want to go this route, you're on your own — and we will not link to grey-market vendors.

Honest takeaway

If you're in midlife and considering peptides:

• For weight loss, the FDA-approved GLP-1/GIP drugs are the strongest evidence-based intervention ever developed. Pair with protein floor + resistance training. Talk to a real prescriber.
• For "longevity peptides" (BPC-157, NAD+, MOTS-c, etc.), the evidence is weak to absent. The marketing is loud. The clinical bar isn't met. Save your money.
• For HGH or HGH-secretagogues — almost universally a bad investment for healthy adults. The downside risk (cancer promotion, glucose intolerance, diabetes) outweighs the modest body comp effect.

Next week: the testosterone-cognition link, for men reading and women whose partners are noticing changes.

Alexander After Forty Feel Reader-funded. Research-led. No supplement-brand sponsorships.