A significant advancement in obesity treatment is on the horizon with the emergence of RES-010, a novel weight loss jab that experts claim could tackle obesity by reprogramming the body's metabolism, potentially obviating the need for dietary changes. This new drug aims to build upon the revolution in obesity treatment brought by blockbuster appetite-suppressing drugs over the last four years, which, despite their effectiveness, often see users regain weight once treatment ceases.

Unlike current treatments that primarily suppress appetite, RES-010 is designed to address the underlying causes of obesity by boosting metabolism. Dr. Ricardo Panella, co-founder and CEO of Resalis Therapeutics, the developer of RES-010, explains that the drug works by blocking a specific molecule in the body called miR-22. This molecule is crucial in controlling how fats are metabolized and how cells utilize and store energy from these fats. By inhibiting miR-22, RES-010 effectively "reprograms how cells handle fat and energy," according to Dr. Panella.

The mechanism involves enhancing the production and activity of mitochondria, often referred to as the "batteries" of cells, and facilitating the conversion of white fat—which stores energy—into brown fat, which actively burns energy. This fundamental metabolic shift is expected to lead to more sustained weight loss, with researchers believing users will be less prone to weight regain after discontinuing the drug, a common challenge with existing treatments. The new fat jab would be the first to tackle the underlying cause of obesity without users needing to eat less, researchers say.

Another promising aspect of RES-010 is its potential to selectively target fat mass while preserving lean muscle, a major concern with current weight loss medications. Studies have indicated that existing drugs can lead to a substantial loss of muscle mass—up to 40% of total weight loss in some cases—along with reduced bone density, increasing risks like osteoporosis. In contrast, preclinical studies showed that obese mice treated with RES-010 lost only 1% of lean mass over ten weeks, compared to 8% in mice given semaglutide (the active ingredient in Wegovy) alone. Furthermore, these mice lost 12% more weight than untreated counterparts despite consuming the same amount of food, and did not regain weight post-treatment, further supporting the claim of metabolic reprogramming over appetite suppression.

RES-010 is currently undergoing its first phase of clinical trials in humans, with the initial assessment focusing on drug safety. Participants, including individuals with overweight and obesity, began treatment in November 2024 in the Netherlands, and preliminary findings are anticipated early next year. The study, titled "Reprogramming Obesity," is slated for presentation at the European Association for the Study of Diabetes' (EASD) annual conference in Vienna, Austria.

While the potential of RES-010 is significant, other experts urge caution. Dr. Adam Collines, a professor of nutrition at the University of Surrey not involved in the study, expressed wariness regarding claims of "reprogramming metabolism" and highlighted the need for more mechanistic understanding of its direct effects on fat cells and mitochondrial function, especially as the current findings were conducted by the drug's manufacturers and are not yet peer-reviewed.

The development of RES-010 comes amidst other advancements in obesity management, including new trials for mega-dose versions of existing drugs like Wegovy. Landmark international studies have shown that a triple-strength dose of Wegovy (7.2mg, up from the standard 2.4mg) led to significantly greater weight loss, approaching nearly a fifth of body weight, while maintaining safety. This higher dose could offer a new option for patients who haven't achieved sufficient weight loss with standard treatments, including those with type 2 diabetes, though it also led to more frequent side effects such as nausea, vomiting, diarrhea, and constipation. These parallel developments underscore a dynamic and evolving landscape in the pursuit of effective and sustainable obesity treatments.