Metabolic disorders and type 2 diabetes mellitus (T2DM) are highly prevalent in patients with heart failure (HF). The majority of patients with T2DM suffer from heart failure with preserved ejection fraction (HFpEF), for which specific therapies are missing. Promising results became evident in recent clinical trials demonstrating a reduction in the three major adverse cardiac events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) through therapy with sodium glucose transporter 2 inhibitors (SGLT2i). The underlying mechanisms of this cardioprotective effect are controversially discussed and may include systemic effects such as volume reduction and occurrence of ketone bodies. Also direct effects of SGLT2i on the heart are still under debate, but their investigation is limited by the availability of suitable model systems. In this study, we aimed to establish a cellular model of diabetic cardiomyopathy using human induced stem cell-derived cardiomyocytes (iPSC-CM) to examine the effect of empagliflozin on human cardiomyocytes. Evaluation of different medium compositions revealed that cultivation of iPSC-CM for 10 days under high-glucose conditions (22 mM glucose) in combination with endothelin and cortisol (DCM-medium), but not under high-glucose concentration alone, recapitulated hallmarks of diabetic cardiomyopathy. Changes in iPSC-CM cultured in DCM medium include impaired expression of genes involved in energy metabolism (GLUT1, GLUT4, CPT1B), reduced cell viability, cellular hypertrophy as well as changes in contractile behavior. In contrast, high-glucose conditions did not affect cell viability, contractile function and did not induce hypertrophy of iPSC-CM. Application of the DCM medium to cardiac organoids consisting of cardiac fibroblasts and iPSC-CM demonstrated similar changes in contractile function and strong hypertrophic response. In these experiments, treatment with empagliflozin had no effect on the changes in functionality, viability or hypertrophy induced by the DCM medium. However, further investigations are necessary to fully characterize potential effects of the empagliflozin on the functionality of human cardiomyocytes, such as calcium signaling or electrophysiological function. Overall, our results demonstrate that the cultivation of iPSC-CM in DCM medium induces cellular changes reflecting the phenotype of diabetic cardiomyopathy. Therefore, our model provides a suitable staring point to investigate the activity and the mechanism of drugs on diabetes-induced metabolic and functional changes in iPSC-CM.