PLoS ONE 7 , e40156 (2012)
Here is the cleanest plain-language comparison of semaglutide, tirzepatide, and retatrutide, plus the nuance people usually skip
Pharmacological: Natural GLP-1: Secreted 5-30 minutes after meals, returns to baseline within 2 hours Weekly injection: Sustained elevation for 168 hours with gradual decline Microdosing: Intermediate pattern with regular, smaller peaks The Case Against: Significant Drawbacks 1
In ACHIEVE-1 , the first of seven Phase 3 studies in people with type 2 diabetes, orforglipron reduced A1C by an average of 1.3% to 1.6% across doses compared to placebo at 40 weeks, starting from a baseline of 8.0%
9,12 Additionally, GLP-1RAs activate nitric oxide (NO) synthase expressed in Schlemms canal and the trabecular meshwork, increasing NO production to reduce trabecular meshwork contraction, improving aqueous outflow
The "exercise in a pill" media coverage in mainstream press does not reflect the current state of scientific knowledge: no human clinical trial has been conducted, human pharmacokinetics remain entirely uncharacterized
