This Week at Peak Human: The FDA Drops Testosterone's Black-Box Warning, Plus New Evidence on Creatine, C15:0, CGMs and Protein

A note from Dr. Goel

This week brought one of the more consequential shifts I've seen in testosterone therapy in years: the FDA formally dropped the entire drug class's decade-old cardiovascular black-box warning. Below is the full picture — plus four more things that changed on peakhuman.ai this week, from a creatine evidence refresh to two new deep-dive articles.

— Dr. Sanjeev Goel

🔬 This week's deep dive: The FDA Drops Testosterone's Cardiovascular Warning

For more than a decade, every testosterone product sold in the U.S. carried a black-box warning about heart attack and stroke risk. In February 2025, the FDA removed it — on the strength of the largest cardiovascular safety trial testosterone has ever had. I updated our Testosterone Replacement Therapy evidence page this week to reflect it, and the full picture is more nuanced than the headline suggests.

What the trial actually tested

The TRAVERSE trial (Lincoff et al., NEJM 2023) was a purpose-built cardiovascular safety study — 5,246 hypogonadal men aged 45–80 with elevated cardiovascular risk, randomized to testosterone gel or placebo and followed for a mean of 33 months. It wasn't designed to prove testosterone works; it was designed to settle, once and for all, whether it's dangerous for the heart.

What the research shows

Primary endpoint: Major adverse cardiac events occurred in 7.0% of the testosterone group vs. 7.3% on placebo (hazard ratio 0.96) — non-inferior to placebo, the basis for the FDA's February 2025 label change.

Secondary signals: Atrial fibrillation was modestly higher with testosterone (3.5% vs. 2.4%), along with higher venous thromboembolism and acute kidney injury rates.

Fracture sub-study (Snyder et al., NEJM 2024):* Unexpectedly, clinical fractures were more common with testosterone (3.50% vs. 2.46%; hazard ratio 1.43) — so it should not be used for fracture prevention.

The honest caveats

This clears testosterone of the cardiovascular fear that has shaped prescribing for 15 years — but it's not a green light to use it freely. The fracture finding is genuinely unexpected, and hematocrit, PSA, blood pressure and cardiac rhythm monitoring remain standard of care. These findings apply specifically to men with documented, symptomatic hypogonadism under medical supervision — this is a summary of published trial data, not medical advice or a recommendation to start therapy. Talk to your physician about whether TRT is appropriate for you.

🗂️ Also new on peakhuman.ai this week

Creatine Monohydrate: the brain and aging-muscle evidence gets stronger

I refreshed our creatine evidence page this week. A 2024 meta-analysis of 16 randomized trials found a small but real improvement in memory (effect size 0.31), and a 2025 meta-analysis in adults 50+ found creatine added further gains in lean mass and leg strength on top of resistance training alone. Typical maintenance dosing is 3–5 g/day.

Pentadecanoic Acid (C15:0): promising, but still early

C15:0 — the active ingredient in fatty15 — got an evidence refresh too. In the first human supplementation trial (2024, 200 mg/day for 12 weeks), participants who reached higher blood levels saw larger improvements in liver enzymes and hemoglobin than those who didn't. These are preliminary, post-hoc subgroup findings from a small trial — worth watching, not yet proven.

New article: The Best CGMs of 2026, Compared

Manufacturer accuracy figures cluster between 8.0% and 10.2% MARD, and the two independent head-to-head studies on the market don't even agree on which sensor wins. I also cover a detail that surprises most patients: healthy, non-diabetic adults spend about 30 minutes a day above 7.8 mmol/L — and that's normal, not a red flag.

New article: How Much Protein to Build Muscle?

The famous 1.6 g/kg protein target comes from a regression that didn't reach statistical significance, with a confidence interval spanning 1.03 to 2.20 g/kg. Across 49 trials in 1,863 people, resistance training itself added 27 kg to a one-rep max — the protein supplement on top added 2.5. I break down what the evidence actually supports.

My take: This is a genuine evidence update, not just a label change — the data holds up. I'm now more comfortable discussing TRT for men with confirmed, symptomatic hypogonadism, provided we actively monitor for the fracture and clotting signals TRAVERSE surfaced. If you're curious whether TRT fits your profile, that's exactly the kind of question our testing and optimization programs are built to answer.

If any of this week's updates apply to you — hormone optimization, cardiometabolic testing, or practitioner-grade supplements — here's where to start.

📰 Longevity news worth your minute

Retatrutide's Phase 3 data keep landing. In Eli Lilly's TRIUMPH-2 trial (adults with type 2 diabetes), the triple-agonist peptide produced −20.8% weight change at 80 weeks on the top dose vs. −4.0% on placebo. It remains investigational, with an FDA submission targeted for Q1 2027 — not yet approved or available.

Rapamycin's human data are staying humble. Two recent trials (PEARL, 48 weeks; RAPA-EX-01, 13 weeks) found weekly rapamycin didn't move visceral fat or boost exercise gains in healthy older adults — a useful reminder that rodent lifespan extension hasn't yet translated into measurable human benefit.

⚕️ Important disclaimer

This newsletter is for educational purposes only and is not medical advice. Compounds discussed may be investigational and not FDA-approved. Nothing here is a recommendation to start, stop, or change any treatment. Peptide and metabolic therapies carry real risks and should only be used under qualified medical supervision. Always consult your physician before making health decisions.