The first generation of modern weight-loss medicines copied one gut hormone, GLP-1. The second paired it with a second hormone, GIP. Retatrutide adds a third, glucagon, and the early results show what happens when you work on appetite, metabolism and fat burning at the same time.
Key points
- GLP-1 is the fullness signal: slower stomach emptying and quieter hunger.
- GIP is the metabolic partner: a stronger insulin response and better energy handling in fat tissue.
- Glucagon is the new piece: more energy use and more fat burning in the liver.
- In the phase 3 TRIUMPH-1 trial, average weight loss reached 28.3% at 80 weeks on the highest dose.
- Lilly plans to submit retatrutide to the FDA in the first quarter of 2027.
Three signals, three jobs
GLP-1 (fullness). Slows stomach emptying, raises insulin after meals and quiets hunger signals in the brain. Most people feel full sooner and think about food less.
GIP (metabolic partner). Strengthens the insulin response to food and appears to help fat tissue store and release energy more efficiently. Adding GIP to GLP-1 is what gave tirzepatide its edge over GLP-1-only medicines.
Glucagon (energy use). The surprising piece. Glucagon usually raises blood sugar, but paired with GLP-1 and GIP its main effects are more energy expenditure and more fat burning in the liver. That is the likely reason liver fat falls so sharply in retatrutide studies.
Together, retatrutide lowers how much you eat and raises how much you burn. Earlier drugs worked mainly on the first half of that equation.
What the phase 3 trials show
TRIUMPH-1 (2,339 adults with obesity or overweight, no diabetes): average weight loss of 28.3% at 80 weeks on the highest dose, 25.9% and 19.0% on the lower doses. In a two-year extension for people starting at a BMI of 35 or higher, loss reached 30.3%. Waist size fell by about 24 cm (9.5 inches), with improvements in triglycerides, blood pressure and inflammation markers.
TRIUMPH-2 (type 2 diabetes): up to 20.8% weight loss and an A1C drop of about 1.5 points. TRIUMPH-3 (established heart disease): up to 22.6% weight loss, with triglycerides down 37% and hs-CRP, an inflammation marker, down about half.
The most common side effects were digestive (nausea, diarrhea, constipation, vomiting), and they rose with dose. A tingling or skin-sensation change (dysesthesia) was also reported, mostly mild. Lilly plans to submit retatrutide to the FDA in the first quarter of 2027.
Because retatrutide is not approved, products sold online as retatrutide are not an approved medicine and may be impure or mislabeled.
The part that matters most: keeping muscle
When weight drops this fast, some of it can come from muscle, and muscle is what keeps you strong, mobile and metabolically healthy as you age. That is why the medicine is only half the plan. Resistance training, enough protein and tracking body composition, not just the scale, decide whether you lose fat or lose function.
Where it fits in an IOF plan
Retatrutide would sit inside our metabolic program, which is built around one goal: lose fat, keep muscle, move better.
Where we start now: FDA-approved GLP-1-based medicines (injections such as tirzepatide or semaglutide, or the newer daily pill orforglipron) when a physician assessment shows they fit, a structured strength plan, protein and recovery targets, and body-composition tracking over time. When retatrutide is approved, it becomes another option on that menu for the right patient.
Common questions
What is retatrutide?
Retatrutide is an investigational weekly injection that activates three hormone receptors: GLP-1, GIP and glucagon. It is being studied for obesity, type 2 diabetes and related conditions, and is not yet FDA approved.
How is retatrutide different from tirzepatide or semaglutide?
Semaglutide works on GLP-1. Tirzepatide works on GLP-1 and GIP. Retatrutide adds glucagon, which increases energy use and fat burning in the liver, on top of the appetite effects of the other two.
Can I get retatrutide at the Institute of Function?
Retatrutide is investigational and not FDA-approved; Lilly plans to submit it to the FDA in the first quarter of 2027. Until approval, it is available only through clinical trials, and we can help you look into trial eligibility. Today our metabolic program uses FDA-approved GLP-1 medicines when they fit, together with strength training, protein targets and body-composition tracking.
Related care
What this means for patients
- Retatrutide works on appetite, metabolism and fat burning at the same time, which is why its trial results are so strong.
- Whatever the medicine, protecting muscle with training, protein and measurement is what turns weight loss into better function.
What this does not mean
- It does not mean retatrutide is available today; it is still investigational.
- It does not mean a medicine replaces strength training and nutrition.
Sources
- Retatrutide achieves up to 30.3% average weight loss in phase 3 TRIUMPH-1 trial (AJMC)
Summary of the TRIUMPH-1 phase 3 results, including weight loss by dose, the two-year extension and waist circumference changes.
- Lilly: retatrutide successful in two additional phase 3 obesity trials (PR Newswire, July 23, 2026)
Lilly's announcement of the TRIUMPH-2 and TRIUMPH-3 results and its plan to submit retatrutide to the FDA in the first quarter of 2027.
- FDA approves orforglipron, an oral GLP-1 for adults with obesity (Healio, April 2026)
Report on the FDA approval of orforglipron, a daily oral GLP-1 medicine for obesity.
- Lilly: retatrutide TRIUMPH-2 results in type 2 diabetes and obesity (September 29, 2026)
TRIUMPH-2 80-week results, up to 20.8% average weight loss and A1C reductions of about 1.5 points; Lilly plans to submit to the FDA in the first quarter of 2027.
Educational content only. Treatment decisions require physician evaluation.
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