Renal Outcomes in Type 2 Diabetes: A Review of Cardiovascular and Renal Outcome Trials

The development of chronic kidney disease (CKD) in people with diabetes is commonplace, and is frequently associated with a significant and unfavourable impact on patient outcomes along with a substantial economic burden. With the development of novel classes of drug therapies in diabetes, there has been a recent focus on cardiovascular safety measures, with dedicated cardiovascular outcome trials (CVOTs) carried out for all new diabetes medications. More recently, there has been a growing regulatory view that such trials should report more specific renal outcomes to ensure simpler comparability between drugs and drug classes. This article explores some of the possible mechanisms by which these drugs may improve renal function in people with diabetes, and it reviews important CVOTs that have reported renal outcomes to date. These include CVOTS of sodium-glucose cotransporter-2 inhibitors (EMPA-REG OUTCOME study, CANVAS study, CREDENCE trial, DECLARE-TIMI trial and DAPA-HF study), dipeptidyl peptidase-4 inhibitors (EXAMINE trial, SAVOR-TIMI 53, TECOS trial and CARMELINA trial) and glucagon-like peptide-1 analogues (ELIXA trial, LEADER trial, SUSTAIN-6 trial, PIONEER-6 trial, EXSCEL trial, HARMONY Outcomes study and the REWIND study). Ongoing cardiovascular and renal outcome studies such as Dapa-CKD, EMPA-KIDNEY, EMPEROR-Preserved and EMPEROR-Reduced are also discussed. The heterogeneity of patient characteristics and reported renal outcomes, which hinders comparisons between trials and drug classes, is highlighted. Novel classes of diabetes therapies present an important opportunity for nephroprotection beyond the blockade of the renin-angiotensin-aldosterone system in this high-risk group. Clinicians should be aware of such benefits when prescribing these medications for people with, and possibly those without, type 2 diabetes.