The GLP-1 class is the biggest story in clinical medicine in a generation — and it is being reshaped in real time. We track semaglutide, tirzepatide, retatrutide, oral candidates, the cardiac and renal endpoints, and the framework for thinking about appetite, insulin, and body composition without the wellness fog.
ATTAIN-1, ACHIEVE-3, ATTAIN-MAINTAIN. Eli Lilly's once-daily oral small-molecule GLP-1 cleared a clean Phase 3 sweep — and the FDA approved it April 1, 2026.
Semaglutide, liraglutide, tirzepatide, retatrutide. Mechanism, trial data, side effects, off-label use.
Why it precedes weight gain in most people. HOMA-IR, fasting insulin, what actually moves the number.
What the wearable data actually tells you. Where it's signal, where it's noise, where it's marketing.
The muscle-loss critique, the protein floor, the resistance training requirement, and what the trial data actually shows.
Five criteria, what each one means, the labs to ask for, and why your doctor probably won't volunteer the panel.
Retatrutide, CagriSema, oral orforglipron. What's in Phase 3, what the readouts look like, who they're for.
Mechanism before headlines. Trial endpoints over surrogate markers. Effect size and number-needed-to-treat over relative-risk theater.
What does the drug or intervention bind to? What's the downstream signal cascade? If we can't write the mechanism in two sentences, the protocol is premature.
Weight change is a surrogate. MACE, all-cause mortality, eGFR decline are endpoints. We weight the trial data accordingly.
STEP and SURMOUNT enrolled people with BMI ≥ 30 (or ≥ 27 + comorbidity). Effect estimates do not transplant cleanly to lean populations chasing aesthetic loss.
Every recommendation in this hub is graded across three risk profiles, with the trade-offs of each named. You decide where you live.
STEP, SURMOUNT, SELECT, FLOW. Mechanism. Cardiovascular and renal endpoints. Lean mass concerns. Compounding compounds. The triple agonists coming behind tirzepatide. A tiered framework that takes the data seriously without becoming evangelical about a drug class.
Read the long read →Pharmacology, dosing, contraindications, off-label use, protein targets. Cited and updated when the evidence updates.
Ozempic, Wegovy, Rybelsus. Weekly SC + oral.
Mounjaro, Zepbound. Dual-agonist weekly SC.
Victoza, Saxenda. Daily SC. Older but still relevant.
GLP-1 + GIP + glucagon. Phase 3. Watch this one.
Eli Lilly's non-peptide oral. Phase 3 ongoing.
Cagrilintide + semaglutide. Novo Nordisk's next bet.
The old standard, off-label longevity, the case and the limits.
"Nature's Ozempic"? Mechanism, evidence, the honest comparison.
Vial mg + BAC water + syringe unit-marks. Live math.
Honest energy math. Protein floor for lean-mass preservation.
Titration schedule for GLP-1s, with tier guidance.
Daily grams + per-meal split. Built for GLP-1 cuts and recomp.