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Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta-analysis

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Toyama, Tadashi, Neuen, Brendon L., Jun, Min, Ohkuma, Toshiaki, Neal, Bruce, Jardine, Meg J., Heerspink, Hiddo L., Wong, Muh Geot, Ninomiya, Toshiharu, Wada, Takashi, Perkovic, Vlado·2019·Diabetes, Obesity and Metabolism

DOI 10.1111/dom.13648

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Abstract

Aim: The use of sodium glucose co‐transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta‐analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results: Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (−0.29%; 95% CI, −0.39 to −0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70‐0.94) and heart failure (RR, 0.61; 95% CI, 0.48‐0.78), without a clear effect on all‐cause mortality (HR, 0.86; 95% CI, 0.73‐1.01). These agents also attenuated the annual decline in eGFR slope (placebo‐subtracted difference of 1.35 mL/1.73 m 2 /y; 95% CI, 0.78‐1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53‐0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion: Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.

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Authors: Toyama, T., Neuen, B. L., Jun, M., Ohkuma, T., Neal, B., Jardine, M. J., Heerspink, H. L., Wong, M. G., Ninomiya, T., Wada, T., & Perkovic, V.
Affiliations: UNSW Sydney (AU)
The University of Sydney (AU)
Concord Repatriation General Hospital (AU)
Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen Groningen The Netherlands
Royal North Shore Hospital (AU)
Kyushu University (JP)
Kanazawa University (JP)
Corresponding author: Perkovic, Vlado
ORCID: Toyama, Tadashi
Neuen, Brendon L.
Jun, Min
Ohkuma, Toshiaki
Neal, Bruce
Jardine, Meg J.
Wong, Muh Geot
Ninomiya, Toshiharu
Wada, Takashi
Perkovic, Vlado
Venue: Diabetes, Obesity and Metabolism
Publisher: Wiley
Published: 2019-03-04
Volume: 21
Issue: 5
Pages: 1237-1250
ISSN: 1462-8902 (ISSN-L)
1463-1326
DOI: 10.1111/dom.13648
OpenAlex: W2914038117
Semantic Scholar: c8cec90d787818b74940feb2baa18c4af10c6271
Cited by: 330
References: 104
Citations by year: 2026: 22 · 2025: 38 · 2024: 50 · 2023: 59 · 2022: 50 · 2021: 49 · 2020: 37 · 2019: 23
FWCI: 6.16
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Diabetes Obesity and Metabolism (publishedVersion)
PubMed (publishedVersion)
UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Spiral (Imperial College London) (submittedVersion)
Funders: National Health and Medical Research Council of Australia
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords: SGLT2 inhibitors, type 2 diabetes, chronic kidney disease, cardiovascular outcomes, renal outcomes, albuminuria, estimated glomerular filtration rate decline, heart failure, myocardial infarction, stroke, all-cause mortality, HbA1c, drug safety, drug interactions, adverse events, drug discontinuation, blood pressure, body weight
MeSH terms: Sodium-Glucose Transporter 2 Inhibitors, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Humans, Hypoglycemic Agents, Treatment Outcome, Renal Insufficiency, Chronic

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Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta-analysis

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