Renal Outcomes of Antidiabetic Treatment Options for Type 2 Diabetes-A Proposed MARE Definition

One of the most critical long-term complications of type 2 diabetes is nephropathy, currently termed diabetic kidney disease. Although the prevalence is increasing, renal outcomes are heterogeneously defined. Intensive glucose control is effective for the prevention of microvascular complications, including kidney disease. However, the impact of specific drugs on renal outcome measures such as the incidence of kidney disease, albuminuria, progression to end-stage kidney disease, or death of renal cause remains unclear. Comparison of agents or drug classes is impossible, as renal outcomes are inconsistently defined in trials. Recent publications include more stringent criteria, but use only composite endpoints, which can reveal significant results driven by a single surrogate marker but not clinical events of true relevance to patients. This review discusses renal outcomes related to antidiabetic agents for type 2 diabetes, in an attempt to determine the influence of specific drugs on the incidence of diabetic kidney disease and various renal outcomes. There are marked differences among the various agents, but direct comparisons are difficult due to heterogeneous measures. Statements from Kidney Disease Improving Global Outcomes (KDIGO) or European Renal Best Practice (ERBP) highlight that "standardized outcome reporting is key to achieving evidence-based guidance and improving clinical care for patients." Renal outcome studies including a well-defined, standardized core set of patient-relevant outcomes are needed. Here, we propose to define and establish major adverse renal events (MARE) as the outcome measure for future studies.