Source – Eli Lilly
On June 26, 2023, Eli Lilly and Company announced the release of new Phase II findings for retatrutide, an investigational molecule developed by Lilly for the treatment of obesity. The data, presented at the American Diabetes Association’s 83rd Scientific Sessions and published in The New England Journal of Medicine (NEJM), demonstrate significant weight reduction in adults with obesity and overweight without diabetes.
In the study, participants were treated with different doses of retatrutide (1 mg, 4 mg, 8 mg, or 12 mg) for a duration of 24 weeks. The primary efficacy endpoint was successfully met, showing a mean weight reduction of up to 17.5% (41.2 lb. or 18.7 kg) at 24 weeks. As a secondary endpoint, retatrutide showcased even more substantial results, with a mean weight reduction of up to 24.2% (57.8 lb. or 26.2 kg) at the end of the 48-week treatment period.
Retatrutide demonstrated a safety profile comparable to other incretin-based therapies. The most commonly reported adverse events were mild-to-moderate gastrointestinal side effects, primarily occurring during the dose escalation phase.
“Obesity is a treatable chronic disease with a complex underlying biology. We are now in the midst of a rapidly expanding therapeutic landscape of potential highly effective treatment options for individuals with obesity. Participants treated with the highest dose of retatrutide achieved a mean weight reduction of 24.2%; this translates to an average absolute weight reduction of about 58 pounds over 11 months of the study. Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction efficacy was not yet attained. Longer duration Phase III trials will enable comprehensive evaluation of efficacy and tolerability of this potential pharmacotherapeutic for the treatment of obesity.”
– Ania Jastreboff, MD, Ph.D., Associate Professor of Medicine & Pediatrics, Endocrinology & Metabolism, at Yale School of Medicine; Director, Yale Obesity Research Center (Y-Weight); and co-Director of the Yale Center for Weight Management
Furthermore, treatment with retatrutide resulted in improvements in various cardiometabolic measures, including blood pressure, triglycerides, LDL-cholesterol, total cholesterol, HbA1c, and fasting glucose and insulin levels at both 24 and 48 weeks.
The ongoing TRIUMPH phase III development program is currently investigating the safety and efficacy of retatrutide for chronic weight management, obstructive sleep apnea (OSA), and knee osteoarthritis (OA) in individuals with obesity and overweight.
TRIUMPH-1: randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety in participants without type 2 diabetes who have obesity or overweight, including participants with OSA and OA
TRIUMPH-2: randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety in participants with type 2 diabetes who have obesity or overweight including participants with OSA
TRIUMPH-3: randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety in participants with Class II (BMI ≥ 35 kg/m2 and < 40 kg/m2) or Class III (BMI ≥ 40 kg/m2) obesity and established cardiovascular disease
TRIUMPH-4: randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety in participants who have obesity or overweight with OA
“We believe that combining glucagon receptor agonism with GIP and GLP-1 receptor agonism may be one of the reasons retatrutide showed this level of weight reduction. These phase II data have given us confidence to further explore the potential of retatrutide in phase III trials that will look beyond weight reduction and focus on treating obesity and its complications comprehensively.”
– Dan Skovronsky, M.D., Ph.D., Lilly’s chief scientific and medical officer, and president of Lilly Research Laboratories
