Emerging Role of Sodium–Glucose Co-Transporter 2 Inhibitors for the Treatment of Chronic Kidney Disease

Abstract

Chronic kidney disease is one of the leading causes of morbidity and mortality in the Philippines. It is associated with a growing health burden as many patients progress to end-stage renal disease. Until recently, therapeutic options for the management of chronic kidney disease were limited. Sodium–glucose co-transporter 2 inhibitors offer an alternative therapeutic approach for patients with chronic kidney disease. Several trials have shown renal benefits with sodium–glucose co-transporter 2 inhibitors in patients with cardiovascular disease with and without type 2 diabetes and across a range of estimated glomerular filtration rate levels. In the Philippines, the sodium–glucose co-transporter 2 inhibitors dapagliflozin and canagliflozin are approved for the prevention of new and worsening nephropathy in type 2 diabetes. With emerging treatment options, an urgent need exists for guidance on the management of chronic kidney disease within the Philippines. In this review, we focus on the putative renal-protective mechanisms of sodium–glucose co-transporter 2 inhibitors, including effects on tubuloglomerular feedback, albuminuria, endothelial function, erythropoiesis, uric acid levels, renal oxygen demand, and hypoxia. Furthermore, we discuss the findings of recent large clinical trials using sodium–glucose co-transporter 2 inhibitors in patients with chronic kidney disease and diabetic kidney disease, summarize safety aspects, and outline the practical management of patients with chronic kidney disease in the Philippines.

Keywords:

• chronic renal insufficiency
• diabetic nephropathies
• safety
• sodium-glucose transporter 2 inhibitors

Data Sharing Statement

The data sets used and/or analysed during the current study are available from the corresponding author on reasonable formal request.

Acknowledgments

The authors would like to thank Steven Tresker for medical writing support and Suchita Nath-Sain, PhD, for editorial assistance, both from Cactus Life Sciences (part of Cactus Communications) in accordance with GPP 2022 guidelines. Editorial and post-submission support was provided by Prajakta Nachane from Labcorp Scientific Services and Solutions Private Limited.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Dr. Rey Isidto was the national lead investigator for the DAPA CKD clinical trial. He has received honoraria for speaking engagements from Astra Zeneca, Servier, Corbridge Group and Zydus Healthcare and LG Life Sciences. Romina A. Danguilan reports honoraria, advisory fees, and research grants from Astellas, AstraZeneca, Corbridge, Multi-Product Line, Novartis, and Philippine Council for Health, Research and Development. Oscar Naidas reports honoraria and lecture fees from AstraZeneca and Boehringer Ingelheim. Russell Villanueva reports honorarium for module development and/or speaking engagements from Astellas, Astra Zeneca, Boerhinger Ingelheim, Globo Asiatico, Merck, Nestle Health Science, Novartis Sanofi Aventis and Servier. Layla Paraiso received honorarium from Fibrogen and GlaxoSmithKlein. The authors report no other conflicts of interest in this work.

Additional information

Funding

The preparation of this manuscript and funding of the journal’s article processing charges was supported by AstraZeneca Pharmaceuticals (Phils), Inc, Philippines.