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A translational review on NNMT inhibitor clinical development ( Emerging opportunities for NNMT inhibitor clinical translation , ScienceDirect, 2026) points out that alternative routes like polyamine biosynthesis could compensate for the raised SAM, and that partial rather than total inhibition might even be preferable specifically to avoid triggering those compensatory mechanisms from a chronically imbalanced SAM/SAH ratio

By reducing NNMTs consumption of nicotinamide, research indicates the compound helps preserve the cellular pool of NAD+

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This metabolic shift promotes the breakdown of stored triglycerides and their release for energy use