Home / Retatrutide guide
Prepared by: Research Desk. Sources are linked for verification.
Status: Investigational. Retatrutide is not approved by the FDA or, as far as we know, by any other regulator. See our approval status page.
Retatrutide (LY3437943, developed by Eli Lilly) is the most-searched experimental weight-loss drug in the world. That interest is driven by headline numbers from its trials. Headline numbers are easy to misread, though. This guide goes through the evidence trial by trial: what was measured, in whom, for how long, and what went wrong as well as right.
Contents
How retatrutide works
Retatrutide is a single peptide molecule that activates three hormone receptors:
GLP-1 receptor. This is the target of semaglutide. It reduces appetite, slows stomach emptying and improves insulin release after meals.
GIP receptor. Tirzepatide hits this target in addition to GLP-1. It contributes to metabolic effects through mechanisms still being studied.
Glucagon receptor. Activating it is thought to increase energy expenditure and fat burning in the liver. This third target is what makes retatrutide a “triple agonist”.
The idea is that the three effects add up to more weight loss and more liver-fat reduction than one or two pathways alone.
Phase 2: the results that started the hype
Obesity (NEJM, 2023)
Design: 338 adults with obesity, or with overweight and at least one weight-related condition, were randomized to retatrutide or placebo for 48 weeks [1].
Results: At 48 weeks, mean weight change across the retatrutide groups ranged from −8.7% to −24.2%, versus −2.1% with placebo [1]. Up to 83% of participants in a retatrutide group reached at least 15% weight reduction, compared with 2% on placebo [1].
Safety signals: The most common adverse events were gastrointestinal: nausea, diarrhoea, vomiting and constipation. Heart rate rose in a dose-dependent way, peaked at 24 weeks, and declined afterwards [1].
Caveat: A phase 2 trial of this size is designed to choose doses, not to establish safety in large populations.
Type 2 diabetes (Lancet, 2023)
Design: 281 adults with type 2 diabetes were randomized to retatrutide, placebo or an active comparator (dulaglutide) [2].
Results: HbA1c fell by up to about 2 percentage points at 24 weeks in the retatrutide groups. Body weight fell by up to about 17% at 36 weeks, versus 3.0% with placebo and 2.0% with dulaglutide [2]. Gastrointestinal adverse events affected 35% of participants across the retatrutide groups, with large differences between groups [2].
Liver fat (Nature Medicine, 2024)
Design: A substudy of 98 participants with obesity and at least 10% liver fat [3].
Results: At 24 weeks, liver fat fell by 42.9% to 82.4% across the retatrutide groups, versus essentially no change with placebo. Up to 86% of participants in a retatrutide group reached normal liver fat levels (under 5%) [3]. This is why retatrutide is also being studied for fatty liver disease.
Phase 3: the TRIUMPH program
TRIUMPH-1: obesity (NEJM, September 2026)
Design: 2,339 adults with obesity or overweight were randomized to retatrutide or placebo for 80 weeks. The trial included prespecified groups with knee osteoarthritis and with obstructive sleep apnea [4]. Registry: NCT05929066 [8].
Results:
Mean weight change at 80 weeks ranged from −17.6% to −25.0% across the retatrutide groups, versus −3.9% with placebo [4].
The trial also reported significant reductions in knee-osteoarthritis pain and in sleep-apnea events (the apnea-hypopnea index) in those subgroups. Gastrointestinal events were again the most common side effects [4].
How to read it: The upper 80-week figures are close to the upper 48-week phase 2 figures. That suggests weight loss largely levels off over the second year rather than continuing indefinitely. The full paper reports more detail on discontinuations and adverse events than the abstract. We’ll add a deeper breakdown on a dedicated TRIUMPH-1 page.
TRIUMPH-2: obesity with type 2 diabetes (Lancet, 2026)
Design: 1,152 adults with obesity and type 2 diabetes, followed for 80 weeks [5]. Registry: NCT05929079.
Results: Mean weight change ranged from −11.9% to −18.8% across the retatrutide groups, versus −5.1% with placebo [5]. As with other incretin drugs, people with diabetes lost less weight than in the obesity-only trial.
Adverse events reported [5]:
Event
Retatrutide (range across groups)
Placebo
Diarrhoea
27–34%
13%
Nausea
14–28%
8%
Dysesthesia (abnormal skin sensations)
4–7%
1%
Hypotension (low blood pressure) occurred in up to 6% of participants. Discontinuation because of adverse events was 8–12% in two of the retatrutide groups [5].
Why dysesthesia matters: Abnormal skin sensations, such as tingling or unusual sensitivity, are not a typical feature of earlier GLP-1 drugs. The signal is small but worth watching in future data.
Still to report
TRIUMPH-3 (NCT05882045): obesity with established cardiovascular disease. Completed on the registry. We have not yet found a peer-reviewed results paper [9].
TRIUMPH-4 (NCT05931367): obesity with knee osteoarthritis. Completed on the registry [10].
TRIUMPH-5 (NCT06662383): head-to-head against tirzepatide. Active, not recruiting [11].
Side effects in one place
Across the published trials, the picture is consistent:
Gastrointestinal effects (nausea, diarrhoea, vomiting, constipation) are the most common. They’re dose-related [1][2][4][5].
Heart rate rose in phase 2, peaking around 24 weeks [1]. This has been seen with other incretin drugs, and long-term cardiovascular data (TRIUMPH-3) are pending.
Dysesthesia appeared more often than with placebo in TRIUMPH-2 [5].
Hypotension occurred in a minority of TRIUMPH-2 participants [5].
Long-term safety beyond about 80 weeks has not yet been established.
Retatrutide vs tirzepatide
This is one of the most common searches, so here’s a careful answer. There is no published head-to-head result yet. TRIUMPH-5 is the trial designed to answer the question [11].
Comparing across trials is risky. Populations, durations and analysis methods differ. A large number from one trial (such as TRIUMPH-1’s −25.0% at 80 weeks [4]) can’t simply be set beside a number from another drug’s trial. Only a randomized head-to-head trial can show whether retatrutide produces more weight loss than tirzepatide, and whether it comes with more side effects.
Frequently asked questions
Is retatrutide approved? No. It is investigational. FDA says it cannot be compounded and has not been found safe and effective for any condition [6].
When might it be approved? A May 2026 industry pipeline summary listed an FDA decision as a 2027 event [7]. Our status page tracks confirmed milestones.
Is it a peptide? Yes. It is a synthetic peptide engineered to activate three receptors.
The bottom line
Retatrutide has produced some of the largest average weight reductions seen in obesity-drug trials. The early phase 3 results confirm the phase 2 promise in a much larger population. It also has a familiar, and in some respects broader, side-effect profile. Cardiovascular outcome data and head-to-head comparisons are still pending. Until a regulator approves it, it remains an investigational compound studied in clinical trials.
Glossary of trial terms
Agonist: a molecule that activates a receptor. Retatrutide activates three receptors.
Placebo-controlled: some participants receive an inactive dummy substance, so researchers can separate drug effects from other influences.
Double-blind: neither participants nor investigators know who received the drug, which reduces bias.
Phase 2 vs phase 3: phase 2 trials choose doses in hundreds of people; phase 3 trials confirm efficacy and characterise risks in thousands [1][4].
Primary endpoint: the main outcome a trial is designed to test, such as percentage weight change at a set week.
Estimand: the precise way a trial’s effect is defined. It decides, for example, how people who stop the study drug are counted, which is why the same trial can report two different headline numbers.
Discontinuation due to adverse events: the share of participants who stopped the study drug because of side effects. In TRIUMPH-2 this was 8–12% in two of the retatrutide groups [5].
Registry record: a trial’s public entry on ClinicalTrials.gov, listing its design, outcomes and status before results come in [8][9][10][11].
Where to follow official updates
Trial records on ClinicalTrials.gov show each study’s status, and they’re updated by the sponsor [8][9][10][11]. Peer-reviewed results appear in journals such as the NEJM and The Lancet [4][5].
Last updated: 18 October 2026.
Not medical advice. This page reports published research and regulatory records for information only.