OBJECTIVES: For management of cardiovascular comorbidities in type 2 diabetes mellitus (T2DM)-patients, an appropriate cardiovascular drug treatment is essential; this was implemented in the respective guidelines. However, there is lack of data regarding the real-world treatment adherence to these guidelines. METHODS: In this retrospective analysis, T2DM-prevalent patients with incident diagnosis of ischemic stroke, myocardial infarction, heart failure or coronary artery disease between 01/01/2014 and 31/12/2016 were observed for 12 months. The impact of guideline adherence on mortality was analyzed based on drug-prescription data from AOK PLUS. RESULTS: The 32,916 identified patients (mean age 75.0 years, 54.2% female, Charlson Comorbidity Index 2.6) received at least one prescription of the following respective agent classes in the 12 months before/after index event: 21%/24% insulin, 47%/43% other antidiabetics, 8%/9% VKAs, 12%/32% antiplatelet drugs, 6%/17% NOACs, 55%/62% beta-blockers, 38%/37% calcium-channel blockers, 73%/72% RAAS-inhibitors and 29%/46% lipid-modifying agents. When post-index therapy is compared to guideline recommendations and an appropriate treatment is assumed if ≥50% of the recommended standard dosage was prescribed, only 14% received guideline-adherent treatment. 7,274 (22%) deaths were observed during follow-up. In a multivariate Cox-regression, including age (hazard ratio [HR] 1.04), female gender (HR 0.79) and comorbidities (HR 1.17), non-adherence to guidelines was an independent predictor for worse prognosis (HR 0.25). CONCLUSIONS: Drug treatment of a majority of T2DM-patients with an incident cardiovascular comorbidity did not follow guideline recommendations. This seems to be one reason for high mortality rates in this population, which were found to be substantially higher than in respective clinical trials.