It cuts appetite and nudges your body to burn a bit more, leading to big weight loss.
How people take it
In the main trials, people took 4, 9 or 12 mg as a shot once a week after a slow step-up.
Know this
It's not approved yet, so anything sold outside a trial has no guarantee of purity or dose.
What it is
Retatrutide is an experimental weekly shot made by Eli Lilly that acts like three natural hormones: GIP, GLP-1 and glucagon. Think of it as tirzepatide plus one extra hormone. It has finished several large trials but isn't approved anywhere yet; Lilly has said it plans to file with the FDA in early 2027.
How it works
Two of the hormones cut your appetite and slow your stomach, the same way tirzepatide does. The third, glucagon, nudges your body to burn a bit more energy and pull fat out of the liver. It also raises heart rate somewhat, which is one reason doses go up slowly.
What people use it for
Weight loss
Blood sugar control in type 2 diabetes
Fatty liver
Knee arthritis pain and sleep apnea linked to obesity (studied in trials)
The evidence
Some human studies
The trial data is strong, but it's not approved yet. In a large late-stage trial (TRIUMPH-1), adults with obesity lost about 18%, 24% and 25% of their weight on 4, 9 and 12 mg over 80 weeks, versus about 4% on a dummy shot, while people with type 2 diabetes lost less (about 12–19% in TRIUMPH-2). Safety past about 1.5 years isn't known, and anything sold outside a trial isn't regulated, so purity and dose aren't guaranteed.
Trials ran 40–80 weeks after a slow step-up starting at a low dose
Route
Subcutaneous injection
Why: These are the three long-term doses tested in the big late-stage trials. 9 and 12 mg gave the most weight loss, and 4 mg still gave a lot with fewer side effects.
Phase 2 trial doses
Trial dose
Dose
1–12 mg
How often
Once a week
When
Same day each week
Cycle
48 weeks, starting at 2 mg and stepping up every 4 weeks
Route
Subcutaneous injection
Why: This earlier trial found that starting at 2 mg caused fewer stomach problems than starting at 4 mg. On the higher doses, people were still losing weight at 48 weeks.
Common community range
Reported
Dose
1–8 mg
How often
Once a week
When
Same day each week
Cycle
Ongoing; many start at 1–2 mg and go up no faster than every 4 weeks
Route
Subcutaneous injection
Why: Many people stop going up once their appetite is under control, to limit nausea and a faster heart rate. These ranges haven't been tested outside the trial schedules.
Step-up schedule
Weeks
Dose
1–4
2 mg once a week (phase 2 start dose)
5–8
4 mg once a week
9–12
8 mg once a week (phase 3 used 9 mg as a maintenance dose)
13 on
12 mg once a week (highest dose tested). Each step is optional: stay on the dose that works and is tolerated.
Start at the low end, and change one thing at a time. If you take medication or have a health condition, check with a doctor first.
We may earn a commission from these links. Counts include one syringe and two swabs per dose.
Stay safe
Side effects
Nausea, vomiting, diarrhea or constipation (very common, worse at higher doses and while stepping up)
Low appetite, burping, indigestion
Faster resting heart rate (peaked around 24 weeks in an earlier trial, then eased)
Tingling or unusually sensitive skin, reported in some later trial results
Dehydration, which can strain the kidneys
Possible gallbladder problems (seen with similar drugs)
Possible pancreatitis, a painful swelling of the pancreas (seen with similar drugs)
Low blood sugar when combined with insulin or sulfonylureas
Losing muscle along with fat if you don't get enough protein and strength training
Skip it if
You or a family member had medullary thyroid cancer or MEN 2 (approved drugs like this carry a boxed warning about thyroid tumors)
Pregnant, trying to get pregnant, or breastfeeding
Past pancreatitis
Heart rhythm problems or high blood pressure that isn't under control (it raises heart rate)
Severe problems with your stomach emptying
Type 1 diabetes
Under 18
Interactions
Insulin or sulfonylureas: higher risk of low blood sugar
Other GLP-1 or GIP/GLP-1 drugs (semaglutide, tirzepatide): don't combine
Birth control pills may work less well (shown with tirzepatide); use a backup method while stepping up
Pills that need exact levels: a slower stomach can change how they absorb
Get help right away for swelling of the face or throat, trouble breathing, chest pain, or a spreading, hot, red injection site.
Storage & legal
Storage
Powder: fridge or freezer. Once mixed: fridge, use within about 4 weeks. Keep out of light, and never freeze it once mixed.
Legal status
FDA: Not approved. Investigational drug; Lilly plans to file with the FDA in 2027.
Sport (WADA): Prohibited at all times under S0 (non-approved substances).
Common questions
Is it better than tirzepatide?
People lost more weight on average in trials, but no published trial has compared the two directly yet. It also raises heart rate more and has less long-term safety data.
Why such a slow start?
In an earlier trial, starting at 2 mg instead of 4 mg cut down on nausea and vomiting. Starting high is the most common way people get sick on it.
Can I take it with semaglutide or tirzepatide?
No. It already does what those drugs do, so combining them just piles up side effects.
Sources
Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PubMed 37366315
Jastreboff AM, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. 2026 Sep 29. Online ahead of print. PubMed 42814954
Urva S, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022;400(10366):1869-1881. PubMed 36354040
Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026 Sep 29. Online ahead of print. PubMed 42810372
Bajaj HS, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. 2026;407(10546):2402-2413. PubMed 42250575
Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. 2023;402(10401):529-544. PubMed 37385280