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Aims Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or body mass index (BMI) after five years. Methods Clinical data and blood samples from 460 newly diagnosed type 2 diabetes patients from the Skaraborg diabetes register (SDR) at diagnosis and after 5 years and were analyzed with linear and logistic regressions. Results High BMI at diagnosis and smoking were associated with less reduction of HbA1c i.e. poorer treatment outcome after 5 years. A high HbA1c at baseline predicted a greater reduction of HbA1c and need for insulin treatment. High systolic blood pressure and BMI at baseline were associated with greater reduction. The biomarkers were not associated with increase of blood pressure, HbA1c, BMI or need for insulin treatment. Conclusions Smokers and patients with high HbA1c at diagnosis respond poorer to treatment over 5 years. This highlights the importance of advice for non-smoking and weight reduction and more intensive treatment over time.