OBJECTIVES: The purpose of this study was to evaluate the relationship between the long-acting insulin analogue glargine (GLA) versus Neutral Protamine Hagedorn insulin (NPH) regarding the incidence of diabetic foot syndrome (DFS), myocardial infarction (MI), and ischemic stroke (IS) in type 2 diabetics (T2D) under real-life conditions in Germany. METHODS: A historic cohort study based on a representative German database (IMS® Disease Analyzer) included T2D who started a basal supported oral therapy (BOT) with either GLA or NPH between July 2000 and September 2007 (index date) and who provided continuously documented data between 12 months before and 24 months after initiation of BOT. Data were collected from index date until the occurrence of an event (DFS or MI/IS) or until August 2009. Duration of therapy was ≥ 24 months to demonstrate a potential effect of insulins considered. Therefore, the endpoints were measured as from the second year after index date. The identification of the endpoints was according to ICD-10 codes (MI: I22 and I23; IS: I63 and I64) or the original doctors texts (DFS). Kaplan-Meier curves were generated and compared by log-rank tests. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) for the incidence of DFS and MI/IS. RESULTS: A total of 23,395 T2D fulfilled the inclusion criteria and started a BOT either with GLA (n=9,638) or with NPH (n=13,757). After adjustment for demographic and clinical variables, it could be demonstrated that GLA reduced the relative DFS-risk by 64 % in T2D when compared to NPH (HR=0.611; p=0.0405). Furthermore, GLA decreased the relative MI/IS-risk by 49 % (HR=0.671; p=0.0562). CONCLUSIONS: When compared to NPH, GLA significantly reduces the risk of DFS in T2D under real-life conditions. Additionally, a reduction of the macrovascular events MI/IS was shown with GLA versus NPH. Prospective trials should be conducted to confirm these results.