Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

Priya Vart¹, Ricardo Correa-Rotter², Fan Fan Hou³, Niels Jongs¹, Glenn M Chertow^{4

5}, Anna Maria Langkilde⁶, John J V McMurray⁷, Peter Rossing^{8

9}, C David Sjöström⁶, Bergur V Stefansson⁶, Robert D Toto¹⁰, Walter Douthat¹¹, Elizabeth Escudero¹², Rey Isidto¹³, Dinesh Khullar¹⁴, Harpreet S Bajaj¹⁵, David C Wheeler¹⁶, Hiddo J L Heerspink^{1

17}

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
² The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico.
³ Division of Nephrology, Department of Medicine, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.
⁶ Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
⁷ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
⁸ Steno Diabetes Center Copenhagen, Gentofte, Denmark.
⁹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
¹¹ Department of Nephrology, Hospital Privado Universitario de Cordoba, Cordoba, Argentina.
¹² Division of Nephrology, Hospital Arzobispo Loayza, Cayetano Heredia University, Lima, Peru.
¹³ Healthlink Medical, Dental, Surgical Clinics and Diagnostics Center, Iloilo City, Philippines.
¹⁴ Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital, Saket, New Delhi, India.
¹⁵ LMC Diabetes and Endocrinology, Brampton, Ontario, Canada.
¹⁶ Department of Renal Medicine, University College London, London, UK.
¹⁷ The George Institute for Global Health, Sydney, Australia.

PMID: 35497805
PMCID: PMC9039473
DOI: 10.1016/j.ekir.2022.01.1060

Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

Priya Vart et al. Kidney Int Rep. 2022.

. 2022 Feb 2;7(4):699-707.

doi: 10.1016/j.ekir.2022.01.1060. eCollection 2022 Apr.

Authors

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
² The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico.
³ Division of Nephrology, Department of Medicine, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.
⁶ Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
⁷ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
⁸ Steno Diabetes Center Copenhagen, Gentofte, Denmark.
⁹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
¹¹ Department of Nephrology, Hospital Privado Universitario de Cordoba, Cordoba, Argentina.
¹² Division of Nephrology, Hospital Arzobispo Loayza, Cayetano Heredia University, Lima, Peru.
¹³ Healthlink Medical, Dental, Surgical Clinics and Diagnostics Center, Iloilo City, Philippines.
¹⁴ Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital, Saket, New Delhi, India.
¹⁵ LMC Diabetes and Endocrinology, Brampton, Ontario, Canada.
¹⁶ Department of Renal Medicine, University College London, London, UK.
¹⁷ The George Institute for Global Health, Sydney, Australia.

PMID: 35497805
PMCID: PMC9039473
DOI: 10.1016/j.ekir.2022.01.1060

Abstract

Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region.

Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m² and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America.

Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48-1.00), 0.60 (0.43-0.85), 0.61 (0.43-0.86), and 0.51 (0.34-0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively).

Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.

Keywords: SGLT-2 inhibitor; dapagliflozin; efficacy; regions; safety.

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Figures

**Figure 1**
Cumulative incidence of primary end point by major geographic region. (a) Asia; (b) Europe; (c) Latin America; and (d) North America.

**Figure 2**
Efficacy of dapagliflozin for primary and key secondary end points by major geographic region. eGFR, estimated glomerular filtration rate.

See this image and copyright information in PMC

References

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Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

Affiliations

Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

Authors

Affiliations

Abstract

Figures

References

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous