ABSTRACT The First in Human Mesenteric Visceral Lipectomy (MVL) Clinical Trial will determine the safety and efficacy of large-volume mesenteric visceral fat (VF) removal in human subjects and evaluate the effect of that removal on glycemic control, insulin sensitivity, and body weight in subjects with T2D; the goals of the MVL procedure are to improve glycemic control, improve insulin sensitivity and to reduce body weight in patients with T2D. The MVL procedure employs Medality Medical's Tissue Liquefaction Technology (TLT) to surgically remove approximately 75% of the VF located in the small bowel mesentery in subjects with class one obesity and poorly controlled T2D, who are in a state of insulin resistance pre-operatively as documented by a clamp test. Excess visceral fat (VF) has been strongly linked with the development of insulin resistance and subsequent type 2 diabetes (T2D) in humans; rodent lipectomy studies have demonstrated that this relationship is causal. Surgically removing subcutaneous fat by large volume liposuction has been explored as a treatment approach, but the vast majority of these studies have failed to demonstrate improvement in metabolic outcomes. Therefore, targeting VF depots for removal should be prioritized in order to rapidly and significantly improve metabolic and overall health in humans. The specific visceral fat depot suspected to be the main contributor to insulin resistance and T2D is the mesentery VF depot, it is the largest of the visceral fat depots, and adipokines produced there drain directly into the liver via the portal vein. Due to the heavy vascularization and other delicate structures within and around the mesentery, there have been no feasible surgical methods or technologies that would allow the safe extraction of mesenteric visceral fat from the body. Studies targeting the greater omentum fat depot have been conducted with mixed results, likely because this depot only accounts for a fraction of total VF mass (~5-10%) in an obese human. Thus, targeting the mesentery, where most VF is harbored, is likely required to surgically treat T2D. Related to fulfilling that goal, we had previously developed and commercialized TLT, which is in use for removing cataracts as well as for removing subcutaneous fat depots. TLT's method is a unique, non-cutting patented approach that delivers low levels of thermal and mechanical energy in a stream of warmed, low-pressurized, and pulsed saline, which causes susceptible non-connective tissues to undergo a phase transition from solid to liquid, while connective tissues do not, thus allowing those liquefied tissues to be removed from the body by aspiration. Blood vessels, lymphatic vessels, and nerves have an outermost covering layer made up of connective tissue and are thus protected, thus they are not liquefied and they remain in a solid state, intact and unharmed. Our work has demonstrated we can effectively use TLT to surgically remove a large volume of visceral f...