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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

The present study demonstrated that NNMT inhibitor administered during adipocyte differentiation blocked the accumulation of lipid droplets, suggesting suppressed lipogenesis and programed development of mature adipocytes from pre-adipocyte 3T3-L1 precursor cells (i.e., adipogenesis)