Patients with type 2 diabetes run a high risk for progressive renal function loss. Many interventions have been tested to reduce the risk, but we are nowadays still confronted with a high unmet need. To improve on this unmet need, we will have to change the current strategies in drug discovery, clinical trials and clinical practice. Target finding and the search for new interventions has to change to include more individual mechanistic approaches. Drugs will be selected on basis of finding the “individual” mechanism of renal function loss by looking at renal tissue biopsies or new biomarkers in urine or plasma. To test the promising drugs for clinical efficacy and safety and reduce the unmet need, trial design in type 2 diabetes will have to alter. First, selection of patients at risk for progression of renal function loss will need to be more specific. True progressors need to be identified by switching from classical risk determinants (low eGFR and high albuminuria) to new surrogates like steep eGFR slopes. In addition, the investigational drugs should only continue into registration trials in responder populations: patients that show a good response in the target/surrogate risk marker and no bad responses. This way we will improve the success of hard outcome trials, which has been poor in the past decade. We will reduce the unmet need and reduce the number of patients that are exposed to long term trial treatments without any benefit or even harm. Platform design and basket trials will catch the non-responders and switch them to other investigational drugs with different mechanism of action.Drug registration will be much more directed to the individual patients and will lead to improved individual patient medication advices and improved individual efficacy and safety. We are entering the era of precision medicine in nephrology.