Aims: People with diabetes tend to face a higher risk of stroke. Randomized controlled trials (RCTs) have demonstrated the different outcomes of new glucose-lowering drugs marketed in recent years on cardiovascular outcome events. The effects of glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors on stroke risk were evaluated in published RCTs.
Methods: A search of Embase, Cochrane Library, and PubMed databases identified studies with stroke as an outcome event up to 3 December 2021. Risk ratios for stroke outcomes were analyzed using a fixed-effects model. I2 was used to assess the heterogeneity of the study.
Results: 19 RCTs with 155,027 participants with type 2 diabetes were identified. Pooled analysis showed that compared to placebo, GLP-1 agonists reduced non-fatal stroke by 15 % (RR = 0.85, 95%CI 0.77-0.94, P = 0.002, I2 = 0 %) and total stroke (RR = 0.84, 95%CI 0.77-0.93, P = 0.000, I2 = 0 %) by 16 %. SGLT-2 inhibitors and DPP-4 inhibitors were not significantly associated with lower stroke risk.
Conclusions: This meta-analysis indicates that GLP-1 agonists have potential benefits for stroke. However, further studies are needed if GLP-1 agonists are to be used to reduce the risk of stroke in patients with type 2 diabetes. More research is also needed to investigate the effects of new glucose-lowering drugs on different stroke subtypes.
Systematic review registration: This protocol was registered on the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42022326382).
Keywords: DPP-4 inhibitors; GLP-1 agonists; SGLT-2 inhibitors; Stroke; Type 2 diabetes.
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