A late-stage clinical trial has found that retatrutide, an experimental weight-loss drug, enabled participants with type 2 diabetes to lose up to 25% of their body weight over 80 weeks. The drug, developed by Eli Lilly, targets three hormone pathways involved in appetite control and blood sugar regulation, offering a potential alternative to existing GLP-1 medications like Mounjaro and Wegovy.
The TRIUMPH-2 trial, published in The Lancet, involved 1,152 adults with type 2 diabetes and a BMI over 27. Participants received weekly injections of retatrutide at doses of 4mg, 9mg, or 12mg, alongside diet and exercise guidance. Those on the highest dose lost an average of 24.2% of their body weight, while the 9mg dose group lost 17.3% and the 4mg group lost 12.1%. Comparatively, Mounjaro, a currently available GLP-1 drug, helps users lose about 20.9% of body weight over a similar period.
Researchers noted that retatrutide also improved blood pressure and cholesterol levels, with nearly a third of participants on the highest dose shedding at least 25% of their body weight. The drug’s mechanism involves mimicking GLP-1, GIP, and glucagon, making it the first triple-agonist weight-loss medication in development. Existing drugs like Wegovy and Mounjaro target only one or two of these pathways.
The trial’s findings were presented at the American Diabetes Association’s annual meeting and published in The Lancet. Dr. Susan Spratt, an endocrinologist at Duke Health not involved in the study, called retatrutide “truly an advance in diabetes care,” noting that it could rival bariatric surgery in effectiveness without the surgical risks.
In a separate trial published in the New England Journal of Medicine, retatrutide was tested on non-diabetic individuals with obesity or overweight. Participants in this study lost up to 25% of their body weight over 80 weeks, with some severe obesity cases shedding 30% of body weight after 104 weeks. This represents the most weight loss ever recorded in a medication trial, comparable to the outcomes of bariatric surgery.
Retatrutide is still under regulatory review and has not yet received approval in the UK or the US. If approved, it could become available on the NHS within three years, according to experts. The drug’s development follows a growing demand for effective weight-loss treatments, particularly for individuals with type 2 diabetes, who often struggle to lose weight with existing medications.
Clinical trials for similar drugs, such as semaglutide (Wegovy) and tirzepatide (Mounjaro), have shown weight loss of 10% and 15% respectively in diabetic patients over comparable periods. However, retatrutide’s triple-agonist approach may offer superior results by addressing multiple metabolic pathways simultaneously.
The drug’s potential extends beyond weight loss, with researchers highlighting its impact on blood sugar control, cardiovascular health, and osteoarthritis risk reduction. The TRIUMPH-2 trial is part of a broader effort to address the global obesity epidemic, which affects over 650 million adults worldwide, according to the World Health Organization.
While retatrutide shows promise, experts caution that long-term safety and efficacy data are still needed. Side effects reported in the trial included gastrointestinal issues such as nausea and diarrhea, which are common with GLP-1 medications. The drug’s cost and accessibility, particularly in public healthcare systems, remain unconfirmed pending regulatory decisions.
The findings add to a rapidly evolving landscape of weight-loss drugs, with Eli Lilly and other pharmaceutical companies investing heavily in the development of next-generation treatments. The results of the TRIUMPH-2 trial are expected to influence future clinical guidelines and insurance coverage policies for obesity and diabetes management.