Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

Autor: G. Caleb Alexander, Omar Mansour, Lily Olson, Sonal Singh, James Heyward
Rok vydání: 2019
Předmět:
medicine.medical_treatment
030204 cardiovascular system & hematology
Vascular Medicine
law.invention
0302 clinical medicine
Mathematical and Statistical Techniques
Endocrinology
Randomized controlled trial
Glucosides
law
Medicine and Health Sciences
Randomized Controlled Trials as Topic
Canagliflozin
Multidisciplinary
Statistics
Metaanalysis
Research Assessment
Type 2 Diabetes
Lower Extremity
Research Design
Meta-analysis
Physical Sciences
Comparators
Observational Studies
Medicine
Engineering and Technology
medicine.drug
Research Article
Risk
medicine.medical_specialty
Drug Research and Development
Systematic Reviews
Endocrine Disorders
Science
030209 endocrinology & metabolism
Subgroup analysis
Placebo
Research and Analysis Methods
Amputation
Surgical
03 medical and health sciences
Peripheral Arterial Disease
Internal medicine
medicine
Diabetes Mellitus
Humans
Clinical Trials
Vascular Diseases
Benzhydryl Compounds
Statistical Methods
Sodium-Glucose Transporter 2 Inhibitors
Pharmacology
business.industry
Randomized Controlled Trials
Sulfonylurea Compounds
Amputation
Peripheral Vascular Disease
Relative risk
Metabolic Disorders
Observational study
Electronics
Clinical Medicine
business
Mathematics
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 6, p e0234065 (2020)
ISSN: 1932-6203
Popis: BackgroundThe association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear.PurposeTo systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use.Data sources and study selectionWe searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo.Data extraction and synthesisTwo reviewers independently extracted data.Main outcomes and measuresOur primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.ResultsAfter screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI's 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality.ConclusionsOverall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration.
Databáze: OpenAIRE
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