Chieh-Hsiang Lu1,2,3, Chen-Yi Yang4, Chung-Yi Li5,6, Cheng-Yang Hsieh7, Huang-Tz Ou8,9,10. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan. 2. College of Chinese Medicine, China Medical University, Taichung, Taiwan. 3. Department of Biotechnology, Asia University, Taichung, Taiwan. 4. Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 7010, Taiwan. 5. Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 6. Department of Public Health, China Medical University, Taichung, Taiwan. 7. Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan. 8. Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 7010, Taiwan. huangtz@mail.ncku.edu.tw. 9. Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. 10. Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan. huangtz@mail.ncku.edu.tw.
Abstract
AIMS/HYPOTHESIS: The effect of pioglitazone was compared with that of other second-line glucose-lowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metformin-based dual therapy. METHODS: A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000-2011 from Taiwan's National Health Insurance Research Database and followed to the end of 2013. Primary analyses included 51,415 individuals aged ≥65 years without dementia events in the first year of second-line glucose-lowering treatment. Study subjects were classified into mutually exclusive groups according to various second-line glucose-lowering drugs to metformin. Cox proportional hazards models were applied to assess the time-to-event between propensity score-matched glucose-lowering treatment groups. RESULTS: Individuals aged ≥65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors). Among individuals aged ≥18 years, there was also a decreased risk of dementia in those taking pioglitazone compared with those taking other second-line glucose-lowering drugs. A lower incidence of dementia was found in users of metformin + pioglitazone compared with users of metformin + rosiglitazone. CONCLUSIONS/ INTERPRETATION: Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.
AIMS/HYPOTHESIS: The effect of pioglitazone was compared with that of other second-line glucose-lowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metformin-based dual therapy. METHODS: A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000-2011 from Taiwan's National Health Insurance Research Database and followed to the end of 2013. Primary analyses included 51,415 individuals aged ≥65 years without dementia events in the first year of second-line glucose-lowering treatment. Study subjects were classified into mutually exclusive groups according to various second-line glucose-lowering drugs to metformin. Cox proportional hazards models were applied to assess the time-to-event between propensity score-matched glucose-lowering treatment groups. RESULTS: Individuals aged ≥65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors). Among individuals aged ≥18 years, there was also a decreased risk of dementia in those taking pioglitazone compared with those taking other second-line glucose-lowering drugs. A lower incidence of dementia was found in users of metformin + pioglitazone compared with users of metformin + rosiglitazone. CONCLUSIONS/ INTERPRETATION:Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.
Entities:
Keywords:
Dementia; Glucose-lowering drugs; Pioglitazone; Type 2 diabetes mellitus
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