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

Abstract

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.

Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

“…In this regard, intensive glucose control has been proven to be effective in preventing or delaying the development and progression of DKD [ 5 6 ]. However, the effects of individual antidiabetic drugs on the kidney have been reported to be different [ 7 ].…”

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement

“…More recently, major adverse renal events (MARE) have been proposed as the outcome measure for future studies. MARE includes a set of major morbidity events such as the development of new-onset DKD, reaching ESRD, starting RRT, or receiving a kidney transplant, and mortality [ 77 ].…”

Diabetische Nierenerkrankung (Update 2019)

“…Einige antihyperglykämische Substanzen haben direkte renale Effekte gezeigt, die sich nicht alleine durch die Blutzuckersenkung erklären lassen [56]. Eine Reihe an kardiovaskulären Outcomestudien untersuchte renale Effekte als sekundäre Outcomeparameter:…”

“…Für Pioglitazon werden auch mögliche nephroprotektive Mechanismen (insbesondere antialbuminurische) disku-tiert [74,76,77]. Die Datenlage ist aber insgesamt schwach [56]. Der Glukosidasehemmer Acarbose kann grundsätzlich in allen Stadien der CKD gegeben werden, ab Stadium G4 jedoch nur in seiner niedrigsten Dosis (<50 mg) [71].…”