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Cited by 53Diabetes Treatment and ManagementHeart Failure Treatment and ManagementChronic Kidney Disease and Diabetes

Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials

Open access
Tsai, Wan-Chuan, Hsu, Shih-Ping, Chiu, Yen-Ling, Yang, Ju-Yeh, Pai, Mei-Fen, Ko, Mei-Ju, Tu, Yu-Kang, Hung, Kuan-Yu +3 more·2022·BMJ Open
DOI 10.1136/bmjopen-2021-060655PMC PMC9577928
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Abstract

Objectives: To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. Methods: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI. Results: We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m 2 /year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion. Conclusions: Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD. PROSPERO registration number: CRD42021239807.

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  • Retatrutide treatment results in marked reductions in hepatic lipid content with subgroup analysis showing MASLD resolution in >85% of people.

    “First results from RCTs with the GLP-1/GIP/glucagon triple RA retatrutide indicate unprecedented weight loss (24.2 % body weight reduction in people with obesity) and glucose control (2.16 % HbA1c reduction in people with type 2 diabetes) [119,141] as well as marked reductions in hepatic lipid content with a subgroup analysis showing MASLD resolution in >85 % of people [142,143].”

    From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [143]

    The Results (Study characteristics; page unavailable) list trials of dapagliflozin and empagliflozin, not retatrutide. Searches for retatrutide, hepatic lipid content, liver fat and MASLD resolution found no passage addressing the claimed reduction or the >85% figure. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Tsai, W.-C., Hsu, S.-P., Chiu, Y.-L., Yang, J.-Y., Pai, M.-F., Ko, M.-J., Tu, Y.-K., Hung, K.-Y., Chien, K.-L., Peng, Y.-S., & Wu, H.-Y.
Affiliations
  • Far Eastern Memorial Hospital (TW)
  • National Taiwan Normal University (TW)
  • National Taiwan University (TW)
  • Taipei Municipal YangMing Hospital (TW)
  • National Yang Ming Chiao Tung University (TW)
Corresponding author
  • Peng, Yu-Sen
  • Wu, Hon-Yen
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2022-10
Volume
12
Issue
10
Pages
e060655
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2021-060655
PMC
PMC9577928
OpenAlex
W4306177054
Cited by
53
References
16
Citations by year
2026: 7 · 2025: 9 · 2024: 20 · 2023: 15 · 2022: 2
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Far Eastern Memorial Hospital (FEMH-2021-C-044, FEMH-2022-C-007, FEMH-EX110-11026PI, FEMH-EX111-11026PI)
  • National Health Research Institutes (NHRI-EX110-11026PI, NHRI-EX111-11026PI)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
SGLT2 inhibitors, cardiovascular outcomes, renal outcomes, heart failure hospitalization, cardiovascular mortality, chronic kidney disease, estimated glomerular filtration rate, end-stage renal disease, urinary tract infection, genital tract infection, non-diabetic patients, drug safety, cardiorenal protection, all-cause mortality, acute kidney injury, hypoglycemia, ketoacidosis, hypovolemia, amputation
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucose, Heart Failure, Humans, Sodium, Randomized Controlled Trials as Topic, Sodium-Glucose Transporter 2, Renal Insufficiency, Chronic

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