How does it work?
Most newer molecules in this class target one or two hormone systems. Retatrutide targets three at once. GLP-1 and GIP are gut hormones that affect insulin, appetite and how quickly the stomach empties. The glucagon signal has been added because it can increase the body's energy expenditure and affect how the liver and fat tissue process energy. Researchers are exploring whether this three-part action produces a stronger effect on weight and metabolism than earlier molecules.
Technical mechanism
Triple agonist: GIP receptor, GLP-1 receptor and glucagon receptor simultaneously. Studies have reported reduced appetite via the hypothalamus, increased thermogenesis, improved insulin sensitivity and lipolysis through the glucagon pathway.
What is being researched?
- Body weight and obesity (phase 2 studies with marked weight loss)
- Blood sugar control in type 2 diabetes
- Fat in the liver and fatty liver disease (MASLD)
- Body composition – fat and muscle mass
- Ongoing phase 3 studies in obesity, sleep apnoea and knee osteoarthritis
About the evidence: Several randomised phase 2 studies in humans (published in journals including the New England Journal of Medicine and The Lancet) show a large effect on weight and blood sugar, and phase 3 studies are now under way or recently published. At the same time, the substance is still being tested and has not completed approval as a medicine; long-term effects and safety have not yet been fully mapped, and the studies are largely funded by the manufacturer. The content here is research information, not health advice.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
Weight loss and obesity (phase 2)
A randomised phase 2 study showed substantial weight loss. More recent systematic reviews and network meta-analyses have compared retatrutide with other weight-loss molecules.
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Clinical (human)PubMed· 2023
In this study of adults with obesity, participants received retatrutide or placebo as a weekly injection for 48 weeks. Those who received the highest doses lost the most weight – on average around 24 per cent after 48 weeks, compared with about 2 per cent in the placebo group. The higher the dose, the greater the weight loss. The most common side effects were gastrointestinal complaints, which were mostly mild to moderate and were somewhat reduced with a lower starting dose. Heart rate increased temporarily.
- Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. ReviewPubMed· 2025
This review pooled 19 randomised studies with almost 30,000 adults with overweight or obesity, and compared different medicines for weight loss. Retatrutide and the dual agonists produced the greatest average weight loss (around 11 kg), more than GLP-1 agents alone (around 9 kg). Retatrutide was best at achieving at least 15 per cent weight loss, but also had the highest risk of side effects. Type 2 diabetes resulted in less weight loss. The authors believe the choice of treatment should be tailored to the individual.
- Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials. ReviewPubMed· 2025
This review pooled three randomised studies with a total of 878 patients with obesity. Compared with placebo, retatrutide reduced body weight, body mass index, waist circumference, fasting blood sugar, long-term blood sugar (HbA1c) and blood pressure. No clear difference in side effects was seen between the groups. The authors conclude that retatrutide produced improvements in weight and several metabolic measures, but emphasise that larger and longer studies are needed to confirm the findings.
Type 2 diabetes and blood sugar
A separate phase 2 study investigated retatrutide in people with type 2 diabetes, and more recent phase 3 work and substudies have looked further at blood sugar and body composition.
- 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. Clinical (human)PubMed· 2023
In this study of adults with type 2 diabetes in the USA, the researchers investigated how different doses of retatrutide affected blood sugar, compared with placebo and another diabetes medicine (dulaglutide). Participants received weekly injections, and the main outcome was the change in long-term blood sugar (HbA1c) after 24 weeks. The text available here mainly describes how the study was designed and who took part, and does not report the final results. An earlier study had suggested that retatrutide may lower blood sugar and weight.
- 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. Clinical (human)PubMed· 2026
In this phase 3 study of 537 adults with type 2 diabetes that was not adequately controlled with diet and exercise, participants received retatrutide or placebo as a weekly injection for 40 weeks. All doses lowered long-term blood sugar (HbA1c) more than placebo, and the highest doses had the greatest effect. Participants also lost weight – up to around 15 per cent with the highest dose, compared with under 3 per cent with placebo. The most common side effects were mild to moderate gastrointestinal complaints that eased over time.
- Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Clinical (human)PubMed· 2025
In this substudy of adults with type 2 diabetes, the researchers looked at how body composition changed after 36 weeks of retatrutide, compared with placebo and dulaglutide. Fat mass was measured by X-ray (DXA). Those who received higher doses of retatrutide lost the most body fat – around 26 per cent in the 8 mg group – while placebo and dulaglutide produced small changes.
Fatty liver (MASLD)
A randomised phase 2a study explored whether retatrutide reduces fat in the liver in people with metabolism-related fatty liver disease (MASLD).
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Clinical (human)PubMed· 2024
In this substudy, 98 participants with fatty liver (MASLD) and at least 10 per cent liver fat received retatrutide or placebo for 48 weeks. After 24 weeks, liver fat was sharply reduced with retatrutide – by up to around 82 per cent at the highest doses – while it was unchanged with placebo. Many reached normal liver fat (under 5 per cent). The reduction was associated with weight loss and better metabolic measures.
- Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions. ReviewPubMed· 2024
This review summarises drug treatment of fatty liver disease (NAFLD/MASLD), which is closely linked to obesity and type 2 diabetes. The authors describe how clinical trials are conducted and the challenges involved, and review two main strategies: repurposing medicines for diabetes and obesity (including tirzepatide and retatrutide) and developing medicines targeted specifically at the liver. They believe the first approved treatments may be close, and that combination treatment may give better results.
Reviews and ongoing studies
Several review articles summarise the mechanism of action and results, and a separate paper describes the ongoing phase 3 studies (TRIUMPH) in obesity, sleep apnoea and knee osteoarthritis.
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. ReviewPubMed· 2026
This article describes how the TRIUMPH study programme for retatrutide is designed. The programme consists of four large phase 3 studies with over 5,800 participants, and simultaneously investigates efficacy and safety in obesity and two related conditions: obstructive sleep apnoea and knee osteoarthritis. Participants receive weekly injections of retatrutide or placebo, together with a healthy diet and physical activity. The article therefore presents the plan and aims of the studies, not completed results.
- A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity. ReviewPubMed· 2024
This review gives a summary of retatrutide as a possible treatment for obesity. Retatrutide acts on three receptors (GLP-1, GIP and glucagon). The authors refer to phase 2 results that found an average weight loss of around 17 per cent after 24 weeks and 24 per cent after 48 weeks in people with overweight and obesity. They emphasise that current knowledge is based on phase 2 studies, and that larger phase 3 studies are needed to confirm the effect.
- The power of three: Retatrutide's role in modern obesity and diabetes therapy. ReviewPubMed· 2024
This review describes retatrutide, which acts on three receptors (glucagon, GIP and GLP-1) at the same time. The authors summarise that clinical studies in phases 1 to 3 have shown substantial weight loss and better blood sugar control, and that the agent may also affect risk factors for cardiovascular disease and fatty liver. They point out that long-term safety, use in special populations and effects in children still need to be investigated further.