The development of new medicines for Diabetes Type 2 complications has proven to be challenging due to the use of cellular models that recapitulate some subsets of the specific features of the human disease. Herewith, we develop environmentally and genetically driven in vitro models of the condition using human induced pluripotent stem cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from diabetic patients with variable disease progression. In this work, we present the first patient-specific iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of new therapeutic strategies. We conclude presenting a new approach using chemical biology to ultimately elucidate novel mechanisms activating cardiomyocytes repair and regeneration.