Combination therapy for kidney disease in people with diabetes mellitus

Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function. For nearly two decades, renin-angiotensin system inhibitors were the only available kidney-protective drugs. However, several new drug classes, including sodium glucose cotransporter-2 inhibitors, a non-steroidal mineralocorticoid antagonist and a selective endothelin receptor antagonist, have now been demonstrated to improve kidney outcomes in people with type 2 diabetes mellitus. In addition, emerging preclinical and clinical evidence of the kidney-protective effects of glucagon-like-peptide-1 receptor agonists has led to the prospective testing of these agents for DKD. Research and clinical efforts are geared towards using therapies with potentially complementary efficacy in combination to safely halt kidney disease progression. As more kidney-protective drugs become available, the outlook for people living with DKD should improve in the next few decades. Several new drug classes have been demonstrated to improve kidney outcomes in people with diabetes mellitus. Here, the authors examine the evidence for the efficacy and safety of combination treatment to reduce the progression of diabetic kidney disease. Diabetic kidney disease (DKD) is associated with substantial morbidity and cardiovascular mortality, and for nearly two decades, the only kidney-protective treatment for DKD was renin-angiotensin system blockade.Positive kidney outcome data have now been reported for SGLT2 inhibitors, the mineralocorticoid antagonist finerenone and endothelin receptor antagonists.GLP1 receptor agonists have been shown to have beneficial effects on surrogate kidney end points, and a kidney outcomes trial is underway.The advent of novel kidney-protective drugs provides new therapeutic options for people living with diabetes and kidney disease but increases the complexity of treatment decisions for caregivers.Combining drugs may enhance their kidney protective efficacy and could potentially reduce the risk of adverse effects that are associated with specific drug classes.An important goal for the future pharmacological management of DKD is to individualize treatment with optimal drug combinations based on the underlying pathophysiology and guided by tissue or serum biomarkers.