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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
Open accessAbstract
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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“SGLT2 inhibitors are not currently indicated for people with an eGFR lower than 45 ml/min per 1•73 m² in most countries, largely because of insufficient glycaemic efficacy.29”
From SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis (2019) · cites this paper as [29]
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Metadata
- 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
- 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
- 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
- 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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