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Lancet Diabetes Endocrinol. 2020 Jan;8(1):27-35. doi: 10.1016/S2213-8587(19)30384-5.

Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study.

Author information

1
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, Netherlands. Electronic address: h.j.lambers.heerspink@umcg.nl.
2
Maccabi Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel; Tel Aviv University, Tel Aviv, Israel.
3
Statisticon, Uppsala, Sweden.
4
Maccabi Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
5
Diabetes Research Centre, University of Leicester, Leicester, UK.
6
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
7
Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain.
8
Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain; Department of Public Health and Maternal and Child Health, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
9
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
10
Clinical Epidemiology Department, CORESEARCH, Centre for Outcomes Research and Clinical Epidemiology, Pescara, Italy.
11
National Taiwan University, Taipei, Taiwan; National Taiwan University Hospital, Taipei, Taiwan.
12
AstraZeneca, Gaithersburg, MD, USA.
13
AstraZeneca, Cambridge, UK.
14
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA.

Abstract

BACKGROUND:

Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice.

METHODS:

CVD-REAL 3 was a multinational observational cohort study in which new users of SGLT2 inhibitors and other glucose-lowering drugs with measurements of estimated glomerular filtration rate (eGFR) before and after (within 180 days) initiation were identified via claims, medical records, and national registries in Israel, Italy, Japan, Taiwan, and the UK. Propensity scores for SGLT2 inhibitor initiation were developed in each country, with 1:1 matching with initiators of other glucose-lowering drugs. Propensity score included (in addition to other clinical and demographic variables) baseline eGFR and eGFR slope before SGLT2 inhibitor or other glucose-lowering drug initiation. The main outcome measure was rate of eGFR decline (slope) calculated with a linear mixed regression model. Differences in eGFR slope between SGLT2 inhibitors and other glucose-lowering drugs were calculated and pooled. We also assessed a composite outcome of 50% eGFR decline or end-stage kidney disease.

FINDINGS:

After propensity matching, there were 35 561 episodes of treatment initiation in each group, from 65 231 individual patients. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin accounted for 57·9%, 34·1%, 5·7%, 1·4%, 0·5%, and 0·4% of SGLT2 inhibitor initiation episodes, respectively. At baseline, 29 363 (41·3%) of 71 122 initiations were in women, mean age was 61·3 years, mean HbA1c was 72 mmol/mol (8·71%), and mean eGFR was 90·7 mL/min per 1·73 m2. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other glucose-lowering drugs 1·53 mL/min per 1·73 m2 per year, 95% CI 1·34-1·72, p<0·0001). During a mean follow-up of 14·9 months, 351 composite kidney outcomes occurred: 114 (3·0 events per 10 000 patient-years) among initiators of SGLT2 inhibitors and 237 (6·3 events per 10 000 patient-years) among initiators of other glucose-lowering drugs (hazard ratio 0·49, 95% CI 0·35-0·67; p<0·0001). These findings were consistent across countries (pheterogeneity 0·10) and prespecified subgroups.

INTERPRETATION:

In this large, international, real-world study of patients with type 2 diabetes, initiation of SGLT2 inhibitor therapy was associated with a slower rate of kidney function decline and lower risk of major kidney events compared with initiation of other glucose-lowering drugs. These data suggest that the benefits of SGLT2 inhibitors on kidney function identified in clinical trials seem to be largely generalisable to clinical practice.

FUNDING:

AstraZeneca.

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