Sodium-glucose co-transporter-2 inhibitors and major adverse limb events: A trial-level meta-analysis including 51 713 individuals
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 51 participants or records.
Read the paper
Related studies
- Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa
- Global and regional estimates of genital human papillomavirus prevalence among men: a systematic review and meta-analysis
- A methodology for assessing deployment trauma and its consequences in OEF/OIF/OND veterans: The TRACTS longitudinal prospective cohort study
- Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study
- Factors Influencing Primary and Secondary Implant Stability—A Retrospective Cohort Study with 582 Implants in 272 Patients
- Electroacupuncture for Painful Diabetic Peripheral Neuropathy: A Multicenter, Randomized, Assessor-Blinded, Controlled Trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.