Eli Lilly has announced that its new weight-loss drug, retatrutide, has helped participants in a large-scale trial lose significantly more weight than other obesity medications currently on the market. The Indiana-based pharmaceutical company reported that participants receiving the highest dose of retatrutide lost an average of 28.3% of their body weight over 80 weeks.
Trial Results
In the phase three trial, 2,339 adults with obesity or overweight, along with at least one weight-related comorbidity and no diabetes, were randomly assigned to receive retatrutide in doses of 4mg, 9mg, 12mg, or a placebo. Over 80 weeks, those on the highest doses achieved substantial weight loss. Patients taking 12mg lost an average of 70.3lb (28.3%), while those on 9mg lost 64.4lb (25.9%). Even the 4mg dose resulted in an average loss of 47.2lb (19.0%), despite only a single dose-escalation step.
Dr Susan Spratt, an endocrinologist and senior medical director at Duke Health, described the results as unprecedented, stating, "This is the largest weight loss I’ve ever seen in any medication trial."
Comparison with Existing Drugs
The weight loss achieved with retatrutide exceeds that of other popular medications. Eli Lilly's own Zepbound typically leads to 15-20% weight loss over 72 weeks, while Novo Nordisk's Wegovy results in 14-19% loss over 64-72 weeks. Retatrutide, like Zepbound and Wegovy, is a GLP-1 receptor agonist, but it also targets GIP and glucagon receptors, making it a triple hormone receptor agonist. This unique combination helps regulate metabolism, appetite, and energy levels.
Side Effects
Patients reported side effects including nausea, diarrhea, and constipation, with rates increasing with dose. Nausea occurred in 28.6% (4mg), 38.4% (9mg), and 42.4% (12mg) of participants, compared to 14.8% on placebo. Diarrhea affected 25.2%, 34.1%, and 32.0% across doses, versus 13.5% on placebo. Vomiting was reported in up to one in four patients on the highest dose, compared to 4.8% on placebo. Upper respiratory tract infections were also more common in treated groups.
Additional Benefits
Beyond weight loss, retatrutide showed improvements in cardiovascular risk factors such as HDL cholesterol, triglycerides, and systolic blood pressure. Emerging research suggests GLP-1 agonists may also reduce anxiety, depression, and sickness-related work absences.
Dr Ania Jastreboff, lead investigator from Yale School of Medicine, noted that "every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, with those on the highest dose losing on average 30% of their body weight over two years."
