Mechanism
A triple agonist.
Glucagon-receptor activity, which raises energy use and liver fat burning, is added to GIP and GLP-1 effects.
Investigational · Phase 3 complete
Retatrutide
Three receptors. One weekly peptide.
Retatrutide is an investigational triple agonist. It activates the GIP, GLP-1 and glucagon receptors, adding an energy-burning pathway on top of tirzepatide's two.
- Targets
- GIPGLP-1Glucagon
- Dosing schedule
- Once weekly, injected under the skin (in trials)
- Half-life
- About 6 days
- Development code
- LY3437943
Approval status
Not approved anywhere as of November 2026. Lilly plans to apply for US approval in Q1 2027. Until then it is available only within clinical trials, and the Philippine FDA has warned against unregistered retatrutide sold for "research use".
Developed by Eli Lilly and Company.
A support, not a shortcut.
This is not a magic weight-loss elixir. It works alongside a healthier diet and regular exercise, and only with a doctor's prescription and guidance.
Highlights
Get to know Retatrutide.
By the numbers
What the trials measured.
How it works
3 receptors. One molecule.
Retatrutide pairs the two incretin signals with glucagon. On its own, glucagon raises blood sugar — but it also increases energy expenditure and fat burning in the liver. In a single molecule, the incretin effects counterbalance the blood-sugar rise.
GIP receptor
Responds to Glucose-dependent insulinotropic polypeptide
- Boosts insulin release when blood sugar is high
- Influences how fat tissue stores and handles energy
- May add to appetite effects and ease nausea alongside GLP-1 (still being studied)
GLP-1 receptor
Responds to Glucagon-like peptide-1
- Boosts insulin release when blood sugar is high
- Lowers glucagon after meals
- Slows stomach emptying
- Signals fullness to the brain
Glucagon receptor
Responds to Glucagon
- Increases energy expenditure
- Promotes fat burning in the liver
- Raises blood sugar on its own — offset by GIP and GLP-1 activity in a combined molecule
The molecule
Engineered to last.
- Development code
- LY3437943
- Class
- Single peptide, triple agonist (GIP / GLP-1 / glucagon)
- Backbone
- Built on a GIP-based peptide sequence9
- Half-life extension
- Fatty-acid side chain for albumin binding
- Receptor balance
- Most potent at the GIP receptor; less potent than the native hormones at the GLP-1 and glucagon receptors9
- Half-life
- About 6 days9
Research
The key trials.
Phase 2 · Obesity
Phase 2- Who
- 338 adults with obesity, or overweight with a related condition, without diabetes
- How long
- 48 weeks
- Compared
- 1, 4, 8 or 12 mg weekly vs placebo
Average body-weight change of −8.7%, −17.1%, −22.8% and −24.2% by dose, vs −2.1% with placebo.6
- Placebo2.1
- 1 mg8.7
- 4 mg17.1
- 8 mg22.8
- 12 mg24.2
Phase 2 · Type 2 diabetes
Phase 2- Who
- 281 adults with type 2 diabetes
- How long
- 36 weeks
- Compared
- Several doses vs placebo and dulaglutide 1.5 mg
HbA1c fell by up to 2.02 percentage points at 24 weeks; body weight by up to 16.9% at 36 weeks.7
Phase 2a · Liver fat
Phase 2a substudy- Who
- Participants from the obesity trial with fatty liver disease
- How long
- 48 weeks
- Compared
- Liver fat measured by MRI
Liver fat fell by more than 80% on average with 8 and 12 mg, and most participants on those doses reached normal levels.8
TRIUMPH-1
Phase 3- Who
- 2,339 adults with obesity, or overweight with a related condition, without diabetes
- How long
- 80 weeks
- Compared
- 4, 9 or 12 mg weekly vs placebo
Company-reported: average weight loss of 19.0%, 25.9% and 28.3% by dose, vs 2.2% with placebo, for people who stayed on treatment (17.6%, 23.7% and 25.0% counting everyone who started).11
- Placebo2.2
- 4 mg19.0
- 9 mg25.9
- 12 mg28.3
TRIUMPH-2 and -3
Phase 3- Who
- Adults with obesity plus type 2 diabetes (TRIUMPH-2) or cardiovascular disease (TRIUMPH-3)
- How long
- Long-term
- Compared
- Retatrutide vs placebo
Company-reported: up to 20.8% weight loss vs 4.0% with placebo in type 2 diabetes, with HbA1c down by up to 1.6 points; up to 22.6% vs 3.2% in cardiovascular disease.12
TRIUMPH-4
Phase 3- Who
- Adults with obesity and knee osteoarthritis
- How long
- 68 weeks
- Compared
- 9 or 12 mg vs placebo
Company-reported: up to 28.7% average weight loss with 12 mg for people who stayed on treatment (23.7% counting everyone who started), plus less knee pain.10
Safety
What to know about side effects.
Most common
- Nausea
- Diarrhea
- Vomiting
- Constipation
- Decreased appetite
In phase 2, digestive side effects were mostly mild to moderate, more common at higher doses, and reduced by starting at a lower dose.
Watch points from trials6
Heart rate
Dose-related increases in heart rate were seen, peaking around 24 weeks and then declining.
Skin sensations
In TRIUMPH-4, about 21% of people on 12 mg reported dysesthesia: unusual skin sensations such as tingling or sensitivity.
Long-term safety unknown
Larger, longer phase 3 trials are needed to understand rarer risks.
Class risks under study
Risks seen with related medicines, such as gallbladder problems and pancreatitis, are being monitored.
Not an approved medicine
Anything sold as retatrutide outside a clinical trial is unapproved and unregulated.
This is a summary, not a complete list. Only a qualified healthcare professional can say whether a medicine is appropriate for someone.
Timeline
From lab to clinic.
2022
Discovery and first-in-human results published.
Jun 2023
Phase 2 obesity (NEJM) and type 2 diabetes (The Lancet) results published.
2023
Phase 3 TRIUMPH program begins.
2024
Phase 2 liver-fat results published in Nature Medicine.
Dec 2025
Lilly reports the first phase 3 topline results (TRIUMPH-4).
May 2026
TRIUMPH-1, the main obesity trial, reports up to 28.3% weight loss at 80 weeks.
Jul 2026
TRIUMPH-2 and -3 succeed; Lilly plans a US filing in Q1 2027.
Oct 2026
Philippine FDA warns the public against unregistered retatrutide products.
Now
Still investigational. Not approved by any regulator as of November 2026.