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Clinical Question
Do glucagon-like peptide-1 receptor agonists decrease stroke risk in patients with type 2 diabetes at high risk for cardiovascular disease?
Bottom line
In this meta-analysis, the use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at high risk for cardiovascular disease was associated with a decreased risk of nonfatal stroke. 1a
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Unknown/not stated
Setting: Various (meta-analysis)
Synopsis
These authors, 3 of whom reported receiving honoraria from industry, searched PubMed, EMBASE, the Cochrane database, and ClinicalTrials.gov to identify randomized trials of GLP-1 receptor agonists (lixisenatide [Lyxumia or Adlyxin], liraglutide [Victosa], semaglutide [Ozempic or Rybelsus], exenatide [Byetta], albiglutide [Tanzeum, which was taken off the market in 2018], and dulaglutide [Trulicity]) in which the researchers reported stroke outcomes. They used reasonable methods for the inclusion of studies and the assessment of methodologic quality. Ultimately, they included 7 trials with 56,004 patients; each of the aforementioned drugs was studied once (the injectable and oral forms of semaglutide were each studied once). All of the studies were at low risk of bias. The study durations varied from 1.3 years to 5.4 years and the mean baseline glycohemoglobin levels ranged from 7.2% to 8.7%. In all but one of the studies, more than 70% of the patients had pre-existing cardiovascular disease, and between 5.4% and 25.0% of the patients had a prior stroke. Finally, most patients were taking statins (66% to 93%) and many were taking antiplatelet agents (54% to 97%). In all but one study (lixisenatide), the incidence of stroke was lower in the treatment group than in the placebo group. Overall, there was a small relative reduction (15%) in the rate of nonfatal stroke and total stroke (16%) and a nonsignificant reduction in the rate of fatal stroke. The authors were not able to find a significant association with stroke risk and glycohemoglobin lowering or weight loss. The authors looked for, and did not find, significant heterogeneity among the data. These authors, like many, did not report the harms of treatment. Finally, they did not report the data in a manner that allowed me to estimate numbers needed to treat.
Reviewer
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI