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In both patient populations with pre-existing cardiovascular disease, DPP-4 inhibitors are recommended as one possible third-line therapy besides SGLT-2 inhibitors, thiazolidinediones, or insulin, when therapeutic goals are not met with the previous dual combination
Furthermore, therapeutic agents targeting mitochondrial enzymes such as SHMT2, PDH, and CPT1A remain largely in preclinical or early-phase clinical development, with limited data available on optimal delivery strategies, pharmacokinetics, and safety profiles [24]
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