The novel mineralocorticoid receptor antagonist finerenone in diabetic kidney disease: Progress and challenges

Yang, Panpan; Huang, Tianlun; Xu, Gaosi

doi:10.1016/j.metabol.2016.06.001

Cited by 14 publications

(4 citation statements)

References 80 publications

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“…In addition, the DAPA‐CKD and EMPA‐KIDNEY trials showed evidence of renal protection with dapagliflozin and empagliflozin in patients with CKD, which was independent of diabetes status 11,27 . Among nsMRAs, finerenone selectively inhibits mineralocorticoid receptors, which results in reductions in renal inflammation, fibrosis and vasoconstriction 46 . However, these mechanisms could be insufficient for finerenone to have higher benefits than SGLT‐2is; SGLT‐2is not only have mechanisms similar to finerenone, but are also related to glucosuria and natriuresis, which contribute to glycaemic control, weight loss, blood pressure‐lowering and reductions in intraglomerular pressure, as well as fluid overload 47 …”

Section: Discussionmentioning

confidence: 99%

“…11,27 Among nsMRAs, finerenone selectively inhibits mineralocorticoid receptors, which results in reductions in renal inflammation, fibrosis and vasoconstriction. 46 However, these mechanisms could be insufficient for finerenone to have higher benefits than SGLT-2is; SGLT-2is not only have mechanisms similar to finerenone, but are also related to glucosuria and natriuresis, which contribute to glycaemic control, weight loss, blood pressure-lowering and reductions in intraglomerular pressure, as well as fluid overload. 47 Our study found a moderate degree of heterogeneity for MACE and stroke.…”

Section: Discussionmentioning

confidence: 99%

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Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

Nguyen

Nguyen²,

Mital

et al. 2023

Diabetes Obesity Metabolism

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Aim: To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Materials and Methods:We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs).Results: Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001).Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes.Conclusions: SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

Nguyen

Nguyen²,

Mital

et al. 2023

Diabetes Obesity Metabolism

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“…Hence, it can efficiently reduce the concentration of aldosterone and play a role in renoprotection [67]. Furthermore, a large randomized controlled trial (RCT) on the renoprotective effect of finerenone in DKD is currently ongoing (FIDELIO-DKD).…”

Section: Pharmacological Synergistic Effects Of Sglt2 Inhibitors In Dmentioning

confidence: 99%

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease

Zou

Zhou

2017

Cardiovasc Diabetol

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Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin–angiotensin–aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

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“…The greatest impact observed in the HOMAGE trial, which investigated the effects of spironolactone on fibrosis and cardiac function in people with increased risk of developing heart failure was the change in vascular wall fibrosis through a reduction in collagen type 1 alpha 1 chain (COL1A1) [ 57 ]. In addition, it has been demonstrated that MRAs reduce endothelin 1 production and oxidative stress [ 58 ]. Proteomic analyses assessing the effect of spironolactone on plasma protein biomarkers indicated that spironolactone reduced levels of collagen metabolism biomarkers (COL1A1, matrix metalloproteinase 2 and brain natriuretic peptide) [ 32 ] (Fig.…”

Section: The Impact Of Mineralocorticoid Receptor Antagonist Utilizat...mentioning

confidence: 99%

Mineralocorticoid receptor antagonists in cardiovascular translational biology

Chilton,

Silva-Cardoso

2023

Cardiovascular Endocrinology &Amp; Metabolism

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This review examines the role of mineralocorticoid receptor antagonists (MRAs) in cardiovascular biology and the molecular mechanisms involved in mineralocorticoid receptor antagonism. The data discussed suggest that MRAs can play an important role in decreasing the impact of inflammation and fibrosis on cardiorenal outcomes. Evidence derived from major randomized clinical trials demonstrates that steroidal MRAs reduce mortality in patients with heart failure and reduced ejection fraction. Initial positive findings observed in patients with chronic kidney disease and type 2 diabetes (T2D) indicate the possible mechanisms of action of nonsteroidal MRAs, and the clinical benefits for patients with cardiorenal disease and T2D. This article supports the application of basic science concepts to expand our understanding of the molecular mechanisms of action involved in pathophysiology. This approach encourages the development of treatment options before diseases clinically manifest. Video Abstract: http://links.lww.com/CAEN/A42

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The novel mineralocorticoid receptor antagonist finerenone in diabetic kidney disease: Progress and challenges

Cited by 14 publications

References 80 publications

Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease

Mineralocorticoid receptor antagonists in cardiovascular translational biology

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