Effect of new glucose-lowering drugs on stroke in patients with type 2 diabetes: A systematic review and Meta-analysis☆
Introduction
Stroke is the second biggest cause of mortality worldwide (11.6 % of all deaths). About 6.55 million people died from a stroke in 2019, there were 12.2 million incident cases of stroke, 101 million prevalent cases of stroke.1., 2. Diabetes is an independent risk factor for stroke.3 The risk of stroke is twice as high in diabetics as in non-diabetics. Diabetes is also a risk factor for stroke recurrence and a high risk of adverse outcomes after stroke.4., 5., 6. Therefore, in 2008, the US FDA issued guidance that new drugs designed to improve glycemic control in patients with type 2 diabetes need to be tested for cardiovascular (CV) outcome trials (CVOTs) to assess the safety of new antidiabetic drugs.7 In recent years, new glucose-lowering drugs, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been proved not to increase the risk of major adverse cardiovascular events (MACE), and may have a potential cerebrovascular event benefit. The results of a meta-analysis8 suggests that, GLP-1 agonists were discovered beneficial for stroke. However, which class of new hypoglycemic drugs has a greater effect on cerebrovascular events, no direct studies are comparing the effect of the three classes of glucose-lowering drugs on stroke events. Given the aforementioned evidence, a meta-analysis was conducted to include these studies, which used SGLT-2 inhibitors, GLP-1 agonists, or DPP-4 inhibitors in the experimental group and placebo in the control group to assess the effect on the risk of stroke in patients with type 2 diabetes.
Section snippets
Methods
This study is reported following the latest PRISMA2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and registered on PROSPERO (CRD42022326382; https://www.crd.york.ac.uk/PROSPERO/).
Study selection and characteristics
Fig. 1 shows the literature search results. A total of 19 eligible studies involving 155,027 T2DM patients published were identified, which included 5 RCTs of SGLT-2 inhibitors (CANVAS,10 CREDENCE,11 DECLARE–TIMI 58,12 EMPA-REG,13 VERTIS CV14), 8 RCTs of GLP-1 agonists (AMPLITUDE-O,15 ELIXA,16 EXSCEL,17 Harmony,18 LEADER,19 PIONEER 6,20 REWIND,21 SUSTAIN-622), and 6 RCTs of DPP-4 inhibitors (CARMELINA,23 EXAMINE,24 Omarigliptin,25 SAVOR-TIMI 53,26 TECOS,27 VIVIDD28).
Baseline data for patients
Discussion
Analysis of available data from pooled RCTs suggests that treatment with GLP-1 agonists has a positive effect on non-fatal stroke and total stroke in the long term. SGLT-2 inhibitors and DPP-4 inhibitors were neutral on stroke outcome.
Studies have shown that both GLP-1 agonists and DPP-4 inhibitors have neuroprotective effects independent of glycemic control. Their effects on stroke are mediated by affecting stroke-related signaling pathways, such as reducing pro-inflammatory factor production,
CRediT authorship contribution statement
CJ and WG formed the conception and study design. JL and CJ were responsible for data collection, data analysis. JL, WZ, and LL contributed to the manuscript drafting. WZ and WG made significant revisions and supplied improvement suggestions.
Acknowledgments
This work received the following financial support: the Hospital pharmaceutical research project of Jiangsu Pharmaceutical Association Chia Tai Tianqing (TQ2021006) and Nanjing Drum Tower Hospital Clinical Research Special Fund Cultivation Project (2021-LCYJ-PY-33).
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2023, 4th International Conference on Electrical, Communication and Computer Engineering, ICECCE 2023
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Conflict of interest
No potential conflict of interest was reported by the authors.
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These authors contributed equally to this work and should be considered the joint first author.