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Association of GLP-1 Receptor Agonist Use With Cardiovascular Outcomes and Mortality in Japanese Patients With Type 2
Masaya Koshizaka1,2,3, Ryoichi Ishibashi2,4, Tomoki Ishikawa5
1Department of Nutrition and Metabolic Medicine, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan.
Aims:
Large-scale clinical trials have shown multiple effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs); however, similar evidence for Asian patients is limited. Therefore, using a Japanese large-scale claims-based database, the effects of GLP-1RAs on cardiovascular and cerebrovascular events including mortality were compared with those of other glucose-lowering agents.
Materials And Methods:
Patients with type 2 diabetes (T2D) were identified from a claims database of approximately 1.9 million individuals. Those newly prescribed GLP-1RAs between 2014 and 2021 were assigned to the GLP-1RA group, while those initiating other glucose-lowering agents served as controls. The primary outcome was cardiovascular or cerebrovascular events or all-cause mortality. Logistic regression analysis was performed using explanatory variables, and nearest-neighbour propensity score matching was performed between the groups. The period from the initiation of new medication to event occurrence was calculated and analysed using the Cox proportional hazards model, with a maximum follow-up of 38 months.
Results:
Among 469 461 eligible patients, 2401 received GLP-1RAs and 53 946 were controls. After propensity matching, 2147 patients remained in each group. The median follow-up was 12 months. No significant difference was observed in 3-point major adverse cardiovascular events (3-point MACE) (GLP-1RA, 7.08% (n = 152) versus control, 8.20% (n = 176); hazard ratio (HR), 0.920; 95% confidence interval (CI) 0.740-1.143, p = 0.450). However, all-cause mortality was lower in the GLP-1RAs group (5.36% (n = 115) versus 7.36% (n = 158), HR 0.776, 95% CI 0.610-0.987, p = 0.039).
Conclusions:
GLP-1RA showed no association with 3-point MACE difference but showed lower all-cause mortality. These findings possibly reflect residual confounding.
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