Renal effects of sodium–glucose cotransporter-2 inhibitors in patients with type 2 diabetes and renal impairment

Abstract

In patients with type 2 diabetes (T2D), microvascular changes in the kidney often result in diabetic kidney disease (DKD), the progression of which is associated with an increased risk of cardiovascular (CV) and all-cause mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are a newer class of oral glucose-lowering therapies that were associated with significant reductions in the risk of major adverse CV events, CV death, and hospitalization for heart failure compared with placebo in CV outcomes trials (CVOTs) of patients with T2D and established CV disease or varying levels of CV risk. In addition, SGLT-2is reduced the risks of clinically relevant renal outcomes in these large randomized studies, indicating the potential for renoprotective effects in patients with T2D and DKD. This review discussed the non-glycemic effects of SGLT-2is in patients with T2D and renal impairment, including reductions in systolic and diastolic blood pressure, decreases in albuminuria and plasma uric acid, changes in estimated glomerular filtration rate, and minimal changes in electrolytes. Potential mechanisms for the renoprotective effects of SGLT-2is observed in CVOTs were considered, including the likely incremental benefits of SGLT-2is when added to renin-aldosterone-angiotensin system inhibitors (RAASis). The possibility of extending the use of SGLT-2is to patients with non-DKD was also discussed. Although the exact mechanisms by which SGLT-2is improve renal outcomes are not fully understood, they are likely to be multifactorial and additive when these drugs are used in combination with RAASis in patients with DKD.

Combined effects of sodium-glucose cotransporter 2 inhibitor and angiotensin receptor-neprilysin inhibitor on renal function in cardiovascular disease patients with type 2 diabetes mellitus: a retrospective cohort study

“…Renal function is an important factor affecting the long-term prognosis of patients with cardiovascular disease. From the mechanism of drug action, the advantages of combined drug use seem to be based on evidence: 1) The mechanisms by which the two drugs reduce intraglomerular pressure are different and may exert complementary effects; 2) The natriuretic and diuretic effect of SGLT2i may activate the renin-angiotensin-aldosterone (RAAS) system when used alone, but combined use with ARNI may offset this effect; 3) This combination may synergistically block sodium-hydrogen exchanger activity, and the latter activity is stimulated by hyperglycemia, hyperinsulinemia and adipokines, which may promote the occurrence and development of glomerular hyperfiltration and diabetic nephropathy, and at the same time play an important role in the pathophysiology of heart failure ( 18 ). Therefore, it is the focus of this study to explore whether the combination of two drugs can delay the deterioration of renal function more significantly than a single drug in the real world.…”

Treatment of anemia in difficult-to-manage patients with chronic kidney disease

“…The development and progression of diabetic kidney disease (DKD) is caused by microvascular changes in the kidney. 26 Diabetes is also associated with inflammation, which is stimulated and exacerbated by hyperglycemia, dyslipidemia, and arterial hypertension. 27 The added burden of diabetic macrovascular and microvascular sequelae, including glomerular hypertrophy and tubulointerstitial fibrosis, further complicates the management of anemia in patients with DKD.…”

Use of SGLT2 inhibitors during Ramadan: An expert panel statement

“…Several ongoing studies, viz. DAPA-CKD, DIAMOND, and EMPA-KIDNEY, are evaluating the efficacy and safety of SGLT2i in nondiabetic kidney disease patients [52]. The results from these studies will prove valuable, since they may orchestrate the evolution of SGLT2i from being anti-hyperglycemic therapeutic agents to cardiorenal protective agents.…”