Research News
Data focused on new drug therapy innovations to treat obesity were presented at the American Diabetes Association's (ADA) 83rd Scientific Sessions in San Diego, USA, in June. Two of the studies, led by Carel le Roux, Full Professor of Experimental Pathology at UCD School of Medicine and UCD Conway Institute, were also simultaneously published in The Lancet.
This comes at a time when 59% of adults and almost 1 in 3 children in Europe are overweight or have obesity, and over 61 million European citizens are living with Diabetes, some 90% of which cases are Type 2. More than 100 million Americans currently live with obesity, a third of them also having Diabetes, with numbers on both sides of the Atlantic climbing steadily.
“Addressing the twin epidemics of obesity and diabetes is critical to slowing the trajectory of this ongoing public health crisis. We have seen an explosion of promising new research and innovations in this field in recent years,” said Dr Robert Gabbay, chief scientific and medical officer for the ADA. “The studies presented at this year’s annual meeting are game-changers in the way we customise treatment for individuals with obesity and those with Type 2 Diabetes.”
Results from a phase 2 clinical trial of survodutide (also known as BI 456906), a novel dual glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) agonist, showed up to 18.7% weight loss in overweight or obese individuals through a 46-week time frame.
Principal Investigator, Professor Carel Le Roux said: “We are encouraged by the significant weight loss observed in the phase 2 study results which will pave the way for further research. By activating both the glucagon and GLP-1 receptors, survodutide may inhibit both appetite and improve energy expenditure. The findings not only show significant weight loss with increasing doses of survodutide, but we also saw a favorable safety profile, reinforcing the potential clinical benefits.”
The randomized, double-blind, placebo-controlled, dose-finding trial, enrolled 387 participants with a body mass index (BMI) of 27 kg/m2 or higher, who were randomly assigned to receive weekly subcutaneous injections of survodutide at varying doses (0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg) or a placebo for a duration of 46 weeks. The study included a 20-week rapid, bi-weekly dose escalation phase, followed by a 26-week maintenance phase. The primary endpoint was the percentage change in body weight from baseline at week 46, and secondary endpoints included the proportion of participants achieving at least 5%, 10%, or 15% weight loss from baseline at week 46.
The results of the study demonstrated a clear dose-response relationship, with increasing doses of survodutide correlating with greater reductions in body weight. At week 46, participants in the survodutide group achieved substantial weight loss compared to the placebo group. The mean body weight reductions were as follows: 0.6 mg (-6.2%), 2.4 mg (-12.5%), 3.6 mg (-13.2%), and 4.8 mg (-14.9%), compared to -2.8% in the placebo group. At 46 weeks, patients reaching and staying on 4.8 mg survodutide achieved a weight loss of 18.7%. Notably, 82.8% of participants in the 4.8 mg BI 456906 group achieved a weight loss of at least 5% at week 46, compared to only 25.9% in the placebo group.
The study also evaluated the safety profile of survodutide. Adverse events were reported in 90.9% of participants in the survodutide group, with the majority being gastrointestinal in nature. In placebo group, adverse events were reported in 75.3% of participants. However, no unexpected safety concerns were identified over the 46-week study period. Serious adverse event incidence was comparable between the survodutide group (4.2%) and the placebo group (6.5%).
The authors of this study anticipate upcoming Phase III trials and are committed to continuing to explore the potential of survodutide to provide a much-needed treatment option for the billions of people with obesity.
Eli Lilly announced earlier this year that tirzepatide (10 mg and 15 mg) achieved superior weight loss compared to placebo at 72 weeks of treatment in results from the SURMOUNT-2 study, also led by Professor Le Roux.
SURMOUNT-2 is the second global phase 3 clinical trial that evaluated the efficacy and safety of tirzepatide for chronic weight management. The trial evaluated 938 adult participants with obesity or overweight and type 2 diabetes.
Professor Le Roux said: "The SURMOUNT 2 study was the first to show that we can achieve 15% weight loss in patients with diabetes. This will disrupt the disease of diabetes and many patients may go into glycaemic remission."
Dr Jeff Emmick, Senior Vice-President for Product Development at Lilly, said: "Obesity is a difficult-to-manage disease, and it's even more difficult for people living with type 2 diabetes. The degree of mean weight reduction seen in SURMOUNT-2 has not been previously achieved in phase 3 trials for obesity or overweight and type 2 diabetes."
For the efficacy estimand, participants taking tirzepatide achieved average weight reductions of 13.4% (29.8 lb. or 13.5 kg) on 10 mg and 15.7% (34.4 lb. or 15.6 kg) on 15 mg compared to placebo (3.3%, 7.0 lb. or 3.2 kg). Additionally, 81.6% (10 mg) and 86.4% (15 mg) of people taking tirzepatide achieved at least 5% body weight reduction, the other co-primary endpoint, compared to 30.5% of those taking placebo.
The SURMOUNT-2 results were also presented at the American Diabetes Association's 83rd Scientific Sessions.