Proteinuria in Normotensive Diabetic Patients: ARBs Alone or in Combination of SGLT2i

Overview

Proteinuria is an early marker of diabetic kidney disease and predicts progression to chronic kidney disease and cardiovascular complications. ARBs are proven to reduce proteinuria and slow renal damage, even in normotensive diabetic patients. SGLT2 inhibitors have recently shown additional reno-protective effects, including further reduction in proteinuria and slowing of disease progression. Combining ARBs with SGLT2 inhibitors may provide additive or synergistic benefits. However, there is limited data comparing ARBs alone versus the combination in normotensive diabetic patients. This study will provide evidence on the most effective strategy to reduce proteinuria, potentially lowering morbidity and preventing complications in this population

Diabetes mellitus is a kind of chronic and progressive disease with high prevalence. There will be 629 million diabetic patients by 2045. About 87% to 91% diabetic patients are probably T2DM in high income countries. Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) worldwide and continues to be the major contributor to kidney replacement therapy (KRT). Diabetic nephropathy (DN) refers to kidney damage caused by diabetes, which is one of the most common complications of diabetes. The main manifestations of DN are proteinuria, hypertension, and kidney function damage, which seriously affect the quality of life and long-term survival rate of patients. Currently, common treatments for DN in clinical practice include blood glucose control, blood pressure control and kidney protection therapy. Currently, agents such as ARBs are promising and have good availability to be used in advanced stages of CKD and4. However, the effects of ARBs on kidney outcomes, such as proteinuria unclear. SGLT2i have become the new standard of care for slowing CKD progression in patients with T2DM due to their specific renal and cardiovascular protective effects that are independent of the main metabolic and glucose-lowering effects. Although SGLT2 inhibitors or ARBs have effects on albuminuria- and BP-lowering in patients with DKD, the effects of monotherapy are always unsatisfactory. Considering their complementary mechanisms on the kidneys, theoretically, SGLT2 inhibitors and ARBs should have synergistic action. Recently several studies indicated that the combination of SGLT2 inhibitors with ARBs satisfactorily afforded greater renoprotection than administration of either drug alone. These results demonstrated a long-term control of hyperglycemia and BP, reduction of hyperfiltration and proteinuria.