OBJECTIVES: Surrogates are valid endpoints, when they could reliably predict the causal clinical benefits and harms of a therapy on the clinical endpoint. The importance of beta-cell dysfunction in patients with type 2 diabetes has been increasingly recognized as the decrease in endogenous insulin secretion makes drug therapy difficult. Several new antidiabetic drugs focus on an improvement of beta-cell activity as a tool for therapeutic treatment. In type 1 diabetes even residual C-peptide secretion is associated with reduction of diabetes related complications. A preservation of beta-cell function might be associated with improved outcomes. The objective of this project is to evaluate the relationship between patient-relevant endpoints and the surrogate beta-cell activity. METHODS: We systematically searched the literature databases of the Centre of Reviews and Dissemination, MEDLINE and EMBASE for relevant publications. All systematic reviews, Health Technology Assessments and Randomized Controlled Trials (RCT) published 1990 - 2007 were included. Due to the small number of publications that assessed clinical endpoints modulated by beta-cell activity in type 2 diabetic Caucasians, cohort studies were also recognized. Patient-relevant outcomes were defined according to the German Institute for Quality and Efficiency in Health Care. Beta-cell activity was measured by C-peptide, fasting insulin excretion or HOMA. Only trials were included not aimed to compare therapeutic interventions to preclude bias of bypass pathways to the clinical endpoint. RESULTS: No publications on high level of evidence were identified. Study length of the 17 cohort studies was between 4 - 14 years. Three studies showed a significant association of beta-cell activity with all-cause mortality and three of four studies showed a significant association with cardiovascular mortality. For microvasular and macrovascular endpoints heterogenous results were reported. CONCLUSION: There is some evidence for an association between beta-cell activity and all-cause and cardiovascular mortality. Validity should to be further evaluated in RCTs.