New data arrives from the EASD congress in Milan on the next generation of therapies for diabetes and obesity: from Eli Lilly’s triple agonist retatrutide to Novo Nordisk’s oral semaglutide, up to weekly combinations. An increasingly multi-target revolution, which aims not only at weight and blood sugar levels, but also at cardiovascular and renal protection.
The new generation of drugs for diabetes and obesity The way we deal with two increasingly intertwined chronic diseases is changing. No longer just blood sugar control and weight loss, but interventions capable of acting simultaneously on multiple metabolic mechanisms, also reducing cardiovascular and renal risk. It is one of the most obvious directions to emerge from 62nd congress of the European Association for the Study of Diabetes (EASD)underway in Milan. Among the data that have attracted the most attention are those of retatrutideexperimental molecule developed by Eli Lilly which acts simultaneously on GIP, GLP-1 and glucagon receptors. In the phase 3 TRIUMPH-2 study, presented at the congress and published on The Lancetthe 12 mg dose produced one after 80 weeks average weight loss of 20.8% in people with type 2 diabetes and obesity or overweight. Glycated hemoglobin decreased by up to 1.6 percentage points. “Such a degree of efficacy, combined with the improvement of triglycerides, waist circumference and markers of inflammation, suggests the possibility of acting simultaneously on multiple aspects of cardiometabolic disease,” observes Stefano Del PratoAffiliate Professor of the Sant’Anna University School of Pisa. Furthermore, with the highest dose more than half of participants reached a BMI no longer diagnostic of obesity. However, Retatrutide remains an experimental molecule and is not yet available to patients.
A combined action against diabetes
However, its development shows what the next leap in metabolic pharmacology could be: moving from single targets to combined action. The change also concerns drugs that have already entered clinical practice. Even the semaglutide has accumulated evidence in recent years that goes beyond the reduction of blood sugar and weight, also showing effects on cardiovascular and renal risk. «Today we no longer limit ourselves to evaluating glycemic control, but we increasingly aim at the prevention of complications and organ protection», he underlines Salvatore De Cosmonational president of the Association of Diabetologists. The data recalled by the expert show reductions in major cardiovascular events, non-fatal stroke and renal risk. But the novelty also concerns the method of administration. In the OASIS 4 study, the oral semaglutide produced by Novo Nordisk produced an average weight loss of 17% at 64 weeks in participants who completed treatment. «Semaglutide in pill form represents one of the most awaited innovations», he explains Roberto Vettorscientific director of the Center for Metabolic and Nutrition Diseases of the Humanitas Research Hospital in Milan. The oral formulation can offer “an alternative to injection therapy” to people eligible for treatment. The possibility of taking the drug by mouth thus adds an element to the personalization of obesity therapymaking the treatment more easily compatible with different needs and preferences.
Insulin and semaglutide together, only once a week
Two drugs, only one injection and only once a week. It is the perspective opened by IcoSemathe fixed combination of insulin icodec and semaglutidedesigned to simplify the treatment of type 2 diabetes. The idea is to combine two complementary mechanisms in the same treatment: on the one hand basal insulin, which guarantees continuous blood sugar control; on the other side semaglutidewhich acts on the regulation of blood sugar and contributes to the reduction of body weight. Studies in the series COMBINEpresented in the EASD scientific program, evaluated this strategy, even in patients already treated with insulin, with the aim of obtaining good metabolic control by reducing the burden of daily therapy. It’s an important change of perspective: not just new drugs, but simpler therapies to followwhich could make it easier to manage a chronic disease that often requires lifelong treatment.
It’s not just how many kilos you lose that matters
This is perhaps the most important passage to emerge from the EASD congress. The effectiveness of an obesity therapy cannot be measured on scales alone. “In the management of overweight and obesity, the evolution of treatment has paved the way for the personalization of care.” explains the President of the Italian Obesity Society, Prof Silvio Buscemi. «The two administration options – oral and injectable – will allow us to guarantee greater flexibility to respond to different needs, always focusing on the safety and efficacy demonstrated by semaglutide. And in this sense, the data on weight loss (21%) and on the quality of weight loss (84% is made up of fat mass) as well as the maintenance of muscle function guarantee a weight loss that is not only significant in quantitative terms, but also of quality. The future of obesity therapy does not simply consist in having new drugs, but in having increasingly effective and customizable solutions, capable of addressing the complexity of obesity and of considering, in addition to weight, people’s metabolic, cardiovascular, psychological health and quality of life“. The quality of weight loss, the preservation of muscle mass, metabolic control and the effects on organs also count. The same logic applies to diabetes: lowering blood sugar levels is necessary, but increasingly less sufficient to define the success of a therapy. From Milan therefore comes a precise photograph of the new metabolic medicine: multi-target molecules, oral formulations, weekly therapies and a growing focus on cardiovascular and renal protection. The challenge is no longer just finding the drug capable of making you lose more weight or lower your blood sugar levels more. . The challenge of the future is increasingly personalized: finding the right therapy for the right personeffective enough to modify the course of the disease and simple enough to be followed over time.
