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Effect of New Glucose-Lowering Drugs on Stroke in Patients With Type 2 Diabetes
TAKE-HOME MESSAGE
- This systematic review and meta-analysis investigated the effect of GLP-1 agonists, SGLT2 inhibitors, and DPP-4 inhibitors on stroke risk in patients with type 2 diabetes. A total of 19 randomized controlled trials with 155,027 participants with type 2 diabetes were included in the analysis. A pooled analysis showed that GLP-1 agonists reduced the rates of nonfatal stroke and total stroke by 15% and 16%, respectively, compared with placebo. SGLT2 inhibitors and DPP-4 inhibitors were not significantly associated with stroke risk.
- GLP-1 agonists may have potential benefits for stroke in patients with type 2 diabetes; however, further studies are needed to see if GLP-1 agonists can be used to decrease the risk of stroke in this patient population.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersAIMS
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Effect of new glucose-lowering drugs on stroke in patients with type 2 diabetes: A systematic review and Meta-analysis
J Diabetes Complicat 2023 Jan 01;37(1)108362, J Li, C Ji, W Zhang, L Lan, W GeFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Trials conducted between 2015 and 2019 showed that two new class of medications, the GLP-1 receptor agonists and SGLT2 inhibitors, reduced the risk for MACE (ie, stroke, myocardial infarction, cardiovascular death) in patients with type 2 diabetes (T2D) and established vascular disease or high risk for the same. The GLP-1 receptor agonists work primarily to prevent stroke and myocardial infarction (presumably mostly by effects on atherosclerosis). The SGLT2 inhibitors work primarily to prevent CVD and heart failure (presumably mostly by hemodynamic effects). Professional guidelines recommend these agents for suitable patients with T2D.
The trial-level meta-analysis by Li et al compares the effect of GLP-1 receptor agonists, SGLT2 inhibitors, and DPP4 inhibitors on stroke alone, a major cause of death and disability worldwide. The meta-analysis includes 19 trials and is well designed and executed. The trials enrolled patients with T2D who had established vascular disease, high risk for vascular disease or CKD. The results show that GLP-1 receptor agonists are associated with a 16% relative risk reduction for fatal or non-fatal stroke and a 15% relative risk reduction for non-fatal stroke. No effect was seen for fatal stroke. Neither SGLT2 inhibitors nor DPP4 inhibitors had any effect on stroke, positive or negative.
These findings may help patients weight the risks and benefits of specific diabetes therapy; when prevention of stroke is paramount, GLP-1 receptor agonists may be the best choice. None of the trials included in this meta-analysis were designed to test secondary prevention in patients with stroke. Because patients with a first stroke and T2D are at very high risk for a second event, trials of secondary stroke prevention are needed.