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Cited by 57Diabetes Treatment and ManagementPeripheral Artery Disease ManagementDiabetes Management and Research

Sodium-glucose co-transporter-2 inhibitors and major adverse limb events: a trial-level meta-analysis including 51 713 individuals

Huang, Chen‐Yu, Lee, Jen‐Kuang·2020·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.14159
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Abstract

Aim To analyse large-scale cardiovascular outcome trials of sodium-glucose co-transporter-2 (SGLT-2) inhibitors to evaluate whether there are safety concerns with respect to major adverse limb events overall or among various high-risk subgroups of patients. Methods We performed a quantitative meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials of SGLT-2 inhibitors in patients with type 2 diabetes. We searched the PubMed, Embase and Cochrane databases for trials published up until 30 June 2020. The efficacy outcomes analysed included amputations and were stratified by several subgroup variables, including age, duration of diabetes, glucose control, renal function, established peripheral artery disease and diabetes microvascular complications. This review was registered before completing the analysis. Results Among 383 records identified, six studies assessing the following three SGLT-2 inhibitors met our inclusion criteria: empagliflozin (EMPA-REG OUTCOME study), canagliflozin (CANVAS Program and CREDENCE study), dapagliflozin (DECLARE-TIMI 58 and DAPA-HF trials) and ertugliflozin (VERTIS CV study). Of a total of 51 713 participants, 858 required amputation operations. The event rates of amputation were 2.0% (535/26 778) and 1.3% (323/24 927) in the SGLT-2 inhibitor and control groups, respectively. The random effects model revealed that SGLT-2 inhibitors were not significantly associated with an increased risk of amputation with substantial heteroge…

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  • Meta-analyses have suggested significant heterogeneity across trials, with increased risk of amputation limited to the CANVAS trial and no increased risk associated with the SGLT2i class overall.

    “Meta-analyses have suggested signi fi cant heterogeneity across trials, with increased risk of amputation limited to the CANVAS trial and no increased risk associated with the SGLT2i class of medications overall.”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [113]

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Authors
Huang, C., & Lee, J.
Affiliations
  • Tao Yuan General Hospital (TW)
  • National Taiwan University (TW)
Corresponding author
Lee, Jen‐Kuang
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2020-09-09
Volume
22
Issue
12
Pages
2348-2355
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.14159
OpenAlex
W3046392970
Cited by
57
References
6
Citations by year
2026: 6 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 3
FWCI
6.41
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Taiwan University Hospital (109‐S4579, 109‐EDN11, 108EDN02, 109‐O20, 107‐EDN11, 108‐N4406)
  • Ministry of Science and Technology, Taiwan (MOST 109‐2221‐E‐002 ‐083 ‐, MOST 108‐2221‐E‐002‐163‐)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
SGLT2 inhibitors, major adverse limb events, amputation, type 2 diabetes, peripheral arterial disease, critical limb ischemia, drug safety, empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, cardiovascular outcome trials, diabetic microvascular complications, renal function, glycemic control, diabetes duration
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Glucose, Humans, Sodium, Multicenter Studies as Topic, Symporters

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