In the context of an aging population with increasing diabetes prevalence, people are living longer with diabetes, which leads to increased multimorbidity and economic burden.The primary aim was to explore different strategies that address the economic impact of multiple type 2 diabetes-related complications and their interactions.We used a generalized estimating equations approach based on nationwide statutory health insurance data from 316,220 patients with type 2 diabetes (baseline year 2012, 3 years of follow-up). We estimated annual total costs (in 2015 euros) for type 2 diabetes-related complications and, in addition, explored different strategies to assess diabetes-related multimorbidity: number of prevalent complications, co-occurrence of micro- and macrovascular complications, disease-disease interactions of prevalent complications, and interactions between prevalent/incident complications.The increased number of complications was significantly associated with higher total costs. Further assessment of interactions showed that macrovascular complications (e.g., chronic heart failure) and high-cost complications (e.g., end-stage renal disease, amputation) led to significant positive effects of interactions on costs, whereas early microvascular complications (e.g., retinopathy) caused negative interactions. The chronology of the onset of these complications turned out to have an additional impact on the interactions and their effect on total costs.Health economic diabetes models and evaluations of interventions in patients with diabetes-related complications should pay more attention to the economic effect of specific disease interactions. Politically, our findings support the development of more integrated diabetes care programs that take better account of multimorbidity. Further observational studies are needed to elucidate the shared pathogenic mechanisms of diabetes complications.