Abstract Background Diabetes (T2DM), heart failure (HF) and chronic kidney disease (CKD) are among the leading causes of mortality and hospitalization worldwide. This analysis of the Ricerca e Salute (ReS) database is aimed to describe clinical epidemiology, 2-year outcomes and direct costs of T2DM patients with HF, CKD or both in a community setting. Methods Analyses were performed on the ReS database including 7,365,716 subjects. During 2015, subjects with T2DM were selected and subsequently split in the following mutually exclusive cohorts (Figure): – “healthy” T2DM patients, subjects with T2DM but without coronary artery disease (CAD), HF, stroke, TIAs, peripheral artery disease (PAD) and CKD. – Patients affected by T2DM and HF. – Patients affected by T2DM and CKD. – Patients affected by T2DM and both HF and CKD. Results Table shows the baseline characteristics, hospitalization reasons, and related costs of the 4 cohorts. In the 2-year follow-up, T2DM patients with comorbidities are older, more frequently males, and more often admitted for CV and renal reasons. T2DM patients with both HF and CKD have the worst outcome profile. The cost per patient per year is 5 times more for T2DM patients with both HF and CKD than for those with T2DM without these comorbidities. Conclusions Coexistence of HF and/or CKD in patients with T2DM ia associated with a very high clinical and economical burden. Instead of treating each condition individually, the most appropriate approach should be to adopt a collaborative approach that embraces CV, renal and metabolic diseases. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was partially supported by an unrestricted grant from Astra Zeneca. Astra Zeneca was not involved in data collection, analysis and interpretation, in writing the report, nor in deciding to submit the article for publication.