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Triple receptor agonist retatrutide demonstrates significant weight loss in phase 2 trial

28th June 2023

Retatrutide gave rise to substantial reductions in body weight in adults with obesity, according to a recent phase 2, randomised placebo-controlled trial.

Retatrutide (formerly LY3437943) is an agonist for the glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptors. In a phase 1b trial, the drug was shown to produce robust reductions in glucose and bodyweight. In addition to drugs such as semaglutide, it is being explored as a treatment for weight loss.

Continuing to explore the value of the drug, in a recent phase 2 trial published in the New England Journal of Medicine, researchers undertook a double-blind, randomised, placebo-controlled trial in adults with a body mass index (BMI) of 30 or more, or those with a BMI of 27 but with at least one weight-related condition.

The trial randomised participants to subcutaneous retatrutide at doses of 1 mg, 4 mg, 8 mg and 12 mg or placebo, administered once weekly for a total of 48 weeks. The primary endpoint was the percentage change in body weight from baseline to week 24, and researchers also assessed the safety of the drug.

In addition to treatment, all the participants received a lifestyle intervention, including regular counselling sessions delivered by a dietitian or qualified healthcare professional.

Retatrutide and weight loss

A total of 338 participants with a mean age of 48.2 years (48% female) were enrolled and randomised to the different doses or placebo.

After 24 weeks of treatment, weight loss ranged from -7.2% in the 1 mg group through to -17.5% in the 12 mg group, compared to -1.6% in the placebo group. However, at week 48, weight loss increased to -24.2% in the 12 mg group compared to -2.1% in the placebo arm. In addition, at week 48, among those receiving 12 mg of retatrutide, 26% of participants had a body-weight reduction of 30% or more.

Treatment with retatrutide also improved cardiometabolic measures including systolic and diastolic blood pressure, glycated haemoglobin, fasting glucose, insulin and lipids – except for high-density lipoprotein. Furthermore, improvements in blood pressure within the 48-week treatment period resulted in discontinuation of at least one antihypertensive medication in 30% of the participants in the 12 mg group.

Adverse events were reported in 70% of the placebo participants and in 73-94% of retatrutide patients. They were highest in the 8 and 12 mg groups. Serious adverse events occurred in 4% of the retatrutide placebo groups.