Eli Lilly’s Retatrutide Called “the Most Powerful Weight-Loss Drug to Date” in Phase 3 Results

September 30 (IT Home) — The technology news outlet Ars Technica published a post today (September 30) reporting that retatrutide, a triple receptor agonist developed by Eli Lilly, is “the most powerful weight-loss drug to date.”

The company’s description is as follows:

Retatrutide is a once-weekly triple hormone receptor agonist still in development. It activates the body’s glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon receptors.

Yesterday (September 29), Eli Lilly published the results of the phase 3 TRIUMPH-1 clinical trial of retatrutide in the New England Journal of Medicine. The trial began in 2023 and enrolled 2,339 participants — adults who were obese or overweight and did not have type 2 diabetes, but who could have other weight-related conditions — across 131 clinical centres in 11 countries. Participants’ average starting weight was 113 kg and their average body mass index (BMI) was 40.

Participants were divided into four groups, receiving 4 mg, 9 mg or 12 mg of retatrutide, or a placebo. The highest-dose group lost an average of 25% of their body weight after 80 weeks, and 30% after treatment was extended to 104 weeks. Overall, more than one third of the participants taking retatrutide lost more than 30% of their body weight.

Beyond weight loss, the drug showed multiple health benefits in subgroup analyses. Among 574 patients with knee osteoarthritis, knee pain was reduced by up to 62%; among 243 patients with obstructive sleep apnoea, the number of apnoea events per hour fell by up to 57%.

Subgroup analysis is a statistical method commonly used in clinical trials and epidemiological research. It means dividing the overall study population into several subgroups according to particular characteristics — such as age, sex, disease severity, coexisting conditions or dosage — and then assessing how the effects of an intervention differ between those subgroups.

In the retatrutide trial, researchers carried out subgroup analyses on specific groups such as patients with knee osteoarthritis, patients with obstructive sleep apnoea and patients with prediabetes, to check whether the drug was equally effective in patients with these coexisting conditions and to quantify the size of the benefits.

On safety, the trial results show that retatrutide is similar to existing GLP-1 and GLP-1/GIP drugs. The most common side effects were transient mild-to-moderate gastrointestinal symptoms, including nausea, diarrhoea and constipation.

Some participants reported dizziness and low blood pressure, which was more common among those also taking blood-pressure medication. There were 10 cardiovascular events and 10 reports of pancreatitis in the trial, and larger trials will be needed to assess rare risks.

As for the trial’s limitations, it did not directly compare retatrutide with existing therapies such as tirzepatide. How it performs relative to existing drugs in terms of weight loss and other health benefits will need to be explored further in future trials.

IT Home checked public information: Eli Lilly’s official account published the research results for the triple receptor agonist retatrutide today. It added that the TRIUMPH-2 study — the results above are from TRIUMPH-1 — showed that participants with obesity and type 2 diabetes who received 12 mg of retatrutide lost an average of 22.5 kg (20.8%) over 80 weeks, and that more than half of the participants no longer had a BMI that met the diagnostic threshold for obesity.

TRIUMPH-2 focused on adults who were obese or overweight and also had type 2 diabetes, with a sample size of 1,152 people. The tests were all 80 weeks long — randomised, double-blind and placebo-controlled — and compared once-weekly subcutaneous injections of retatrutide (4/9/12 mg) with a placebo, alongside diet and exercise.