28 Jun 2023 • Retatrutide, an investigational once-weekly injectable triple agonist helped patients with obesity lose an average of 24% of their body weight over 48 weeks on the highest dose in a mid-stage study, the most weight loss seen yet in a new class of drugs that’s revolutionizing the field. The study was published Monday in the New England Journal of Medicine & the results also presented at the ADA 2023 conference in San Diego.

KEY POINTS

• The Triple–Hormone-Receptor Agonist Retatrutide for Obesity Phase 2 Trial was designed to look at the efficacy and safety of retatrutide for the treatment of obesity
• The study evaluated 338 participants with obesity who did not have T2D; they were randomized to receive either 1 mg, 4, mg, 8 mg, or 12 mg doses of retatrutide or to a mock drug (placebo) for 48 weeks.
• Findings demonstrated that participants with obesity lost more than 24% of their starting body weight within 48 weeks of treatment with the highest dose of retatrutide
• Among 281 randomized people with overweight or obesity and type 2 diabetes, the same dose of retatrutide produced a nearly 17% cut in weight from baseline after 36 weeks of treatment.
• Findings also showed that participants with T2D lowered their HbA1c by 1.3% to 2.0% after taking 4-12 mg retatrutide for about six months, compared to no change with placebo and a 1.4% HbA1c reduction with dulaglutide
• The phase 2 obesity study included a NAFLD substudy, evaluated 98 patients with obesity and NAFLD who underwent MRI of their livers and had biomarkers of liver injury and fibrosis measured in their blood.
• Findings showed that in those with NAFLD, the amount of fat in the liver normalized in 9 out of 10 patients after 48 weeks treatment with the two highest doses of retatrutide.

As a next step, the TRIUMPH phase 3 program will evaluate the safety and efficacy of retatrutide for chronic weight management, obstructive sleep apnea, and knee osteoarthritis in people with obesity and overweight.

Source: NEJM | Read full story