• Yongjun Sunwoo, Jaeho Park, Chang-Young Choi, Sooyoung Shin, and Yeo Jin Choi.
• Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea; Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Korea; Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Korea.
• Am J Prev Med. 2024 Sep 1; 67 (3): 434443434-443.

IntroductionDementia risk is substantially elevated in patients with diabetes. However, evidence on dementia risk associated with various antidiabetic regimens is still limited. This study aims to comprehensively investigate the risk of dementia and Alzheimer's disease (AD) associated with various antidiabetic classes.MethodsCochrane Central Register of Controlled Trials, Embase, MEDLINE (PubMed), and Scopus were searched from inception to March 2024 (PROSPERO CRD 42022365927). Observational studies investigating dementia and AD incidences after antidiabetic initiation were identified. Bayesian network meta-analysis was performed to determine dementia and AD risks associated with antidiabetics. Preferred Reporting Items for Systematic Reviews-Network Meta-Analyses (PRISMA-NMA) guidelines were followed. Statistical analysis was performed and updated in November 2023 and March 2024, respectively.ResultsA total of 1,565,245 patients from 16 studies were included. Dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i). Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk. SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas, and thiazolidinediones (TZD) compared to SGLT2i in the elderly (≥75 years). Dementia risk associated with metformin was substantially lower, regardless of diabetic complication status or baseline A1C.DiscussionMetformin and SGLT2i demonstrated lower dementia risk than other antidiabetic classes. Patient-specific factors may affect this relationship and cautious interpretation is warranted as metformin is typically initiated at an earlier stage with fewer complications. Hence, further large-scaled clinical trials are required.Copyright © 2024 Elsevier Inc. All rights reserved.

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