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The weight-loss plateau observed with potent incretin mimetics such as semaglutide and tirzepatide reflects a phenomenological constraint: as body mass declines, the rate of mass outflow declines, and the mass clearance coefficient k decreases due to metabolic adaptation. Dynamic Energy Balance Models (EBMs) describe the kinetics of this plateau by modeling appetite feedback, but they do not resolve the physical scaling constraint that limits total mass loss. The Mass Balance Model (MBM) provides this constraint via a phenomenological square-root scaling law. To overcome this limit, we propose pairing a central NMI-reducing agent (Component A) with a peripheral NMO-stabilizing or enhancing agent (Component B). Crucially, candidate agents for Component B must be classified by their mass-balance mechanism: SGLT2 inhibitors increase NMO via urinary glucose excretion; mitochondrial uncouplers increase NMO via respiratory gas exchange; activin/myostatin pathway inhibitors do not increase NMO but shift mass partitioning toward lean tissue. We outline a 72-week randomized controlled trial using co-primary endpoints of total weight loss and DXA-measured fat mass, with a mechanistic sub-study measuring k in a metabolic chamber. The MBM provides a quantitative framework for selecting and evaluating combinations that target both sides of the mass balance equation.