Description
Opinion Only. Not for Medical Reference.
Retatrutide
Retatrutide (reta) is referred to as a “triple agonist”. An “agonist” is a receptor that turns on certain signals in the body, like hunger, insulin release, etc. Reta activates 3 of them: (1) GIP, (2) GLP-1, and (3) Glucagon. The GIP signal helps regulate insulin and appetite. GLP-1 slows digestion and reduces hunger. Glucagon helps influence energy burning and fat metabolism. I think of it as a 3rd generation weight loss peptide, with tirzepatide (Monjouro and Zepbound) the 2nd generation (they only activate GIP and GLP-1), and semaglutide (Ozempic) the 1st generation (it only activates GLP-1).
Reta is currently (Nov 2025) in Phase 3 human trials. Phase 2 trial results were published October 2025 in the New England Journal of Medicine. Here is a link to the phase 2, double-blind, randomized, placebo-controlled trial:
https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
Weight Loss: Results are substantially better than with semaglutide (Ozempic) or tirzepatide (Monjauro). At 48 weeks, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of reta; 100%, 91%, and 75% of those who received 8 mg. The most common adverse events in the reta groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg). Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter.
Other Benefits: Treatment withreta was associated with improvements in cardiometabolic measures (exploratory end points) including systolic and diastolic blood pressure and levels of glycated hemoglobin, fasting glucose, insulin, and lipids (with the exception of high-density lipoprotein [HDL] cholesterol).
Reta has been associated with improvements in lipid profiles, including reductions in triglycerides, LDL, and VLDL cholesterol. It also showed a significant reduction in blood pressure in both T2DM and obese patients.
Reta has also shown potential benefits on kidney function, with significant reductions in urine albumin-to-creatinine ratio (UACR) and increases in estimated glomerular filtration rate (eGFR) in obese patients.
Reta’s ability to influence liver triglyceride concentrations forms another critical area of research. In clinical trials, reta has exhibited a capacity to decrease hepatic fat content, confirming its prospect for treating NAFLD and enhancing overall liver function. Such observations underscore the therapeutic implications of reta beyond mere weight loss into essential metabolic health.
Lilly published their TRIUMPH-4 Phase 3 data in December 2025 for retatrutide.
28.7% weight loss. 71 pounds average. At 68 weeks. Here’s what happened:
445 people with obesity and knee osteoarthritis. Split into three groups – 9mg retatrutide, 12mg retatrutide, and placebo. The 12mg group lost an average of 71.2 pounds. That’s 28.7% of their starting weight. And 8 percentage points higher than tirzepatide’s ~21% in Phase 3.
Other Endorsements: A very interesting endorsement is this one by Dr. Trevor Bachmeyer. He states that in his opinion the weight loss aspects of reta are the least important of the benefits, and he gives compelling reasons for that in this video:
https://youtu.be/3Xjn3aIHi3Y?si=Zo5Dl7kCdtVYevCI
He says that in his opinion semaglutide (Ozempic) and tirzepatide (Monjauro) are trash and should be thrown away, and reta used instead. He talks about “why” in this video:
https://www.youtube.com/watch?v=JJZzjJhP2rQ
Both videos cite many different scientific studies, but the last one probably cites the most.
Dosage: Weekly injection (it has a half life of 8 days)
For obesity, the standard protocol is to start at 2mg per week for one month, and then titrate up from there. I recommend 1.5mg the first week so that you can monitor side-effects, and then 2mg for the next 3 to 5 weeks. Slowly titrate up from there (in 0.5mg increments per week), depending on how you feel. Trials peaked at 12mg per week. Many people don’t see a lot of results until after around 3mg per week.
Dosage is around 0.5mg weekly for people that are not overweight but want other benefits of retatrutide.
16mg vial with 1.6cc BAC = 1mg per 10 units. 16mg vial with 3.2cc BAC = 500mcg per 10 units.
60mg vial with 3cc BAC = 2mg per 10 units. (80mg = 40 units)
