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Review
. 2021 Feb;23(2):299-317.
doi: 10.1111/dom.14251. Epub 2020 Nov 20.

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations

Chin Meng Khoo  1 , Chaicharn Deerochanawong  2 , Siew Pheng Chan  3 , Bien Matawaran  4 , Wayne Huey-Herng Sheu  5 , Juliana Chan  6 , Ambrish Mithal  7 , Andrea Luk  6 , Ketut Suastika  8 , Kun-Ho Yoon  9 , Linong Ji  10 , Nguyen Huu Man  11 , Carol Pollock  12
Affiliations
Review

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations

Chin Meng Khoo et al. Diabetes Obes Metab. 2021 Feb.

Abstract

Early onset of type 2 diabetes and a high prevalence of co-morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin-angiotensin system inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT-2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA-CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT-2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end-stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose-lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.

Keywords: diabetes, diabetic kidney disease, diabetic nephropathy, gliflozins, renal disease, SGLT, type 2 diabetes.

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Conflict of interest statement

CMK has received honoraria as a speaker or advisor from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Sanofi. CD has received honoraria as the speaker or advisor or research grant from AstraZeneca, Boehringer Ingelheim, Janssen, Bayer, Eli Lilly, Abbott, Novartis, Pfizer, Merck Sharp & Dohme, Novo Nordisk, Sanofi and Takeda. SPC has received honoraria as speaker and advisor for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi and Servier. BM has received honoraria and CME grants from AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Multicare, MSD, NatraPharm, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier and Torrent Pharma. WHHS has been advisor and/or speaker for AstraZeneca, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals., Daiichi‐Sankyo, Eli Lilly and Company, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Sanofi‐Aventis and Takeda Pharmaceutical Company. JC is the Chief Executive Officer (on pro‐bono basis) of Asia Diabetes Foundation, a charitable foundation established under The Chinese University of Hong Kong Foundation for developing the JADE Technology; she has received honoraria and travel support for consultancy or giving lectures, and her affiliated institutions have received research and educational grants from Amgen, Ascencia, AstraZeneca, Bayer, Bristol‐Myers Squibb, Boehringer Ingelheim, Daiichi‐Sankyo, Eli‐Lilly, GlaxoSmithKline, Medtronic, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Pfizer and Sanofi. AM has received honoraria as speaker and advisor from AstraZeneca, Abbott, Boehringer Ingelheim, Cipla, Dr Reddyʼs, Eli Lilly, Glenmark, GlaxoSmithKline, Ipca, Janssen, Lupin, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi, Serdia Servier, Sun Pharma, Torrent, Wockhardt and Zydus Nutrition. AL is a member of advisory boards for AstraZeneca, Boehringer Ingelheim, Sanofi and Amgen; she has received research grants from Boehringer Ingelheim, MSD, Sanofi and Amgen, and travel grants from AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk and Sanofi. KS has received honoraria as a speaker or advisor from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Sanofi, Merck and Servier. KHY has received honoraria as a speaker or advisor from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novo Nordisk, Sanofi and Takeda; and research support from AstraZeneca and Takeda. LJ is a member of the DISCOVER Scientific Committee and has received support from AstraZeneca to attend DISCOVER planning and update meetings; he has also received honoraria from Eli Lilly, Bristol‐Myers Squibb, Novartis, Novo Nordisk, Bayer, Merck Sharp & Dohme, Takeda, Sanofi, Roche, Boehringer Ingelheim and AstraZeneca; and research support from Roche, Sanofi, Merck Sharp & Dohme, AstraZeneca, Novartis, Eli Lilly and Bristol‐Myers Squibb. NHM has no disclosures to declare. CP has received honoraria as a speaker or advisor for AstraZeneca, Otsuka, Merck Sharp & Dohme, Boehringer Ingelheim, Eli Lilly, Vifor and Novartis; she is a member of the CREDENCE trial steering committee and has received honoraria from Janssen to compensate for time spent working on the trial steering committee; she is also a director at Certa Therapeutics.

Figures

FIGURE 1
FIGURE 1
SGLT‐2 inhibitors: clinical evidence across the renal disease continuum. C, CANVAS Program; CK, CREDENCE; D, DECLARE‐TIMI56; DK, DAPA‐CKD; E, EMPA‐REG OUTCOME; eGFR, estimated glomerular filtration rate; EK, EMPA‐Kidney; GFR, glomerular filtration rate
FIGURE 2
FIGURE 2
SGLT‐2 inhibitors: mechanism of cardiorenal benefits. Physiological mechanisms implicated in the cardiovascular and renal protection with SGLT‐2 inhibition. BP, blood pressure; DKD, diabetic kidney disease; GFR, glomerular filtration rate; NHE1, sodium‐hydrogen exchanger 1; NHE3, sodium‐hydrogen exchanger 3; SGLT‐2, sodium‐glucose co‐transporter‐2; TGF, tubuloglomerular feedback
See this image and copyright information in PMC

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