ISC 2025 | A meta-analysis of the efficacy of GLP-1 receptor agonists in the prevention of stroke

Good morning guys. Today I am here to discuss the studies that I have presented at the ISC stroke, thanks to VJNeurology and all the team members involved in facilitating this event. So the study is all about the efficacy of the glucagon-like peptide 1 receptor agonists for the prevention of stroke. A meta-analysis of randomized control trials in which we include patients with and without diabetes. I would like to disclose that there is no financial disclosures that any of the doctors have disclosed and no conflict of interest involved in the study. Background. GLP-1 receptor agonist’s analogs are glucose-lowering medications for managing various types of cardiometabolic disease including diabetes and overweight. Glucagon-like peptide 1 receptor agonists has shown to have a reduction in cardiovascular events in previous meta-analysis and even the randomized control trials in patients with type 2 diabetes. However, the efficacy on cerebral vascular events is not well established till date in diabetic and non-diabetic patients. So, we sought to evaluate the efficacy of GLP-1 receptor agonists in the prevention of stroke on patients with and without diabetes. Methodologies. So, we included studies from inception till 15th July 2024, and our inclusion criteria was patients more than 18 years of age with all the included intervention roles for us and having these two arms, one with GLP-1 intervention as an intervention group and placebo as a control group. These studies must have recorded the outcome of interest, that is primary and secondary outcomes, which we will discuss later. Our exclusion criteria were studies performed on animals, various case reports, and studies of single arms are without having outcome of interest. Our primary outcome was a stroke, and secondary outcome was the risk of fatal stroke, non-fatal stroke, adverse events such as systemic stroke, hemorrhagic stroke, embolic stroke, and cerebral vascular events. Statistical analysis, we performed a conventional meta-analysis from primary and secondary outcomes and adopted the DerSimonian and Laird effect model for the study, the variance. Outcomes were reported as a pooled odds ratio and then corresponding 95% confidence interval. The statistical significance was met at 95% confidence does not cross the numeric value 1. And total value of P less than 0.05 was considered a statistical significant result. A pooled analysis of primary, a total of 11 studies were involved in the study in which GLP-1 RA group are having about 43,309 patients and 42,000 patients approximately in the placebo group. The mean age of the GLP-1 RA group was 63.5 years and 63 years in the control group. The median follow-up duration was 2.1 years for the entire duration of the study. Pooled analysis of primary and secondary outcomes show that GLP-1 RAs significantly reduced the incidence of stroke by 15% with an odds ratio of 0.85, 95% confidence interval 0.77 to 0.93, and P value less than 0.001, and non-fatal stroke by 13% risk reduction with an odds ratio of 0.87, 95% confidence interval 0.79 to 0.95, and P value less than 0.001 compared with placebo. However, the risk of total stroke without the ratio of 0.94 was found to be comparable within both the group of patients. Similarly, the risk of serious adverse event such as cerebrovascular accident, although showing non-significant decision but shows a non-significant reduction with the p-value of 0.75 and p-value of 0.05. And hemorrhagic stroke with odds ratio of 0.82 and p-value 0.57 and a ischemic stroke with a also ratio of 0.85 and p-value of 0.26. Although found non-significant reduction, but so is a trend of reduction in favor of GLP-1 R-agonist. Now this central illustration highlights the findings and these are the baseline and favors have all included studies of 11 clinical trials from FLOW, SELECT, EXSCEL, HARMONY, REWIND, PIONEER 6, ELIXA, LEADER, SUSTAIN-6, AMPLITUDE-O, and the rest of the others. And in conclusion, treatment with GLP-1 RA group agonist has a beneficial effect, in reducing the risk of a stroke and non-fatal stroke in patients without diabetes. However no such effect was observed for fatal stroke. And the reason being the no such significant reduction found in fatal stroke is basically GLP1 are associated with reduction in the risk factors associated with the cardiovascular events. That was cardiovascular events. A direct effect was found for reduction in cardiovascular events. And these risk factors play a role in reducing the risk of stroke, or chronic stroke, or any fatal strokes, as well as mortality, we don’t find any cessation because these are like spontaneous, and the risk factors that are involved are not going to be managed immediately by these drugs. Thank you.

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