Preventing and treating kidney disease in patients with type 2 diabetes

ABSTRACT

Introduction: Chronic kidney disease (CKD) represents a huge burden in patients with type 2 diabetes (T2DM). This review therefore has the aim of assessing the add-on value of new glucose-lowering agents compared or combined with inhibitors of the renin angiotensin aldosterone system (RAAS) on renal outcomes in T2DM patients.

Areas covered: This article first summarizes the results reported with RAAS inhibitors, mainstay of nephroprotection in T2DM with albuminuria. Second, it describes the positive results with glucagon-like peptide-1 receptor agonists (GLP-1RAs) and, even more impressive, sodium-glucose cotransporter type 2 inhibitors (SGLT2is). Third, besides the potential of combined therapies, it briefly considers some new approaches currently in development.

Expert opinion: RAAS inhibitors exert renoprotective effects beyond their blood pressure lowering effects while SGLT2is, and possibly GLP-1RAs, exert nephroprotection independently of their glucose-lowering activity. These effects were demonstrated not only on surrogate endpoints such as albuminuria and estimated glomerular filtration rate decline, but also on hard endpoints, including progression to end-stage renal disease requiring replacement therapy. The underlying mechanisms are different and potentially complementary on glomerular hemodynamics, arguing for combined therapies. Nevertheless, there is still room for new emerging drugs to tackle CKD in T2DM.

KEYWORDS:

• Chronic kidney disease
• GLP-1 receptor agonist
• RAS inhibitors
• SGLT2 inhibitor
• Type 2 diabetes

Article Highlights

• Glucose and blood pressure control are essential to prevent CKD in T2DM, an increasing prevalent complication of the disease.

• RAAS blockade, either with ACE inhibitor or ARA II, is the cornerstone of nephroprotection in T2DM, but dual blockade should be avoided for safety reasons.

• Metformin may now be used in patients with CKD (if eGFR > 30 ml/min per 1.73 m²) and might be associated with a reduced risk of progression of renal impairment.

• New glucose-lowering agents, that is, GLP-1RAs and SGLT2 inhibitors, exert renoprotective effects beyond improvement of glucose control, in combination with RAAS blockers, in T2DM patients at high cardiovascular risk.

• Because SGLT2is reduce hard renal outcomes and not only surrogate endpoints (albuminuria) as GLP-1RAs, they are considered as the best option after metformin in T2DM patients with CKD provided that eGFR is adequate.

• RAAS blockers and SGLT2 inhibitors exert different effects that can protect kidney function, yet the complementary effects on intrarenal hemodynamics appear predominant.

• To reduce the residual risk, new medications are in development targeting low-grade inflammation, oxidative stress, and renal fibrosis, as add-on therapies to existing drugs.

This box summarizes key points contained in the article.

Declaration of interest

AJ Scheen has received lecture/advisor fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.