Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort

Kim, Yonghwan; Kim, Hyeong-Seop; Lee, Jae-woo; Kim, Yeseul; You, Hyo-Sun; Bae, Yoon-Jong; Lee, Hyeongcheol; Han, Ye-Eun; Choi, Eun‐A; Kim, Joungyoun; Kang, Hee-Taik

doi:10.1016/j.diabres.2020.108496

Cited by 16 publications

(21 citation statements)

References 31 publications

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“…Nevertheless, this study found the association between NAFLD and an increased risk of dementia in a large cohort whose prevalence of NAFLD was 31%, comparable to that in previous reports 34,35 . The annual incidence rate of dementia among the study population was 1.08% which also corresponds to the rate previously reported 36 . The association of NAFLD and a higher risk of dementia was consistent when clinical variables and competing risk of death were considered.…”

Section: Discussionsupporting

confidence: 90%

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Association between non‐alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study

Kim

et al. 2022

Liver International

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Background and Aims Little is known about the association between non‐alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. Methods We conducted a nationwide cohort study involving 4 031 948 subjects aged 40–69 years who underwent ≥2 health check‐ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non‐NAFLD (HSI <30 at all check‐ups) and NAFLD (HSI >36 at one or more check‐ups). Dementia defined by ICD‐10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. Results At baseline, 31.3% had NAFLD. During the median follow‐up of 9.5 years, 138 424 in NAFLD group and 69 982 in non‐NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non‐NAFLD group on multivariable‐adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity‐score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non‐obese NAFLD subjects (BMI <25 kg/m2, HR, 1.09; p < .001) than obese NAFLD subjects. Conclusions This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non‐obese NAFLD subjects.

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Section: Discussionsupporting

confidence: 90%

“…34,35 The annual incidence rate of dementia among the study population was 1.08% which also corresponds to the rate previously reported. 36 The association of NAFLD and a higher risk of dementia was consistent when clinical variables and competing risk of death were considered. Yet, there has been a study showing a conflicting result.…”

Section: Discussionmentioning

confidence: 83%

Association between non‐alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study

Kim

et al. 2022

Liver International

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“…Sixty‐nine articles were read in full. Finally, 12 population‐based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non‐users) were eligible for inclusion in this meta‐analysis 14‐25 …”

Section: Resultsmentioning

confidence: 99%

“…Table 1 presents the baseline characteristics of included studies. Among the studies published between 2011 and 2020, seven studies 14,15,20‐24 were from Asia, four studies 16‐18,25 were from the United States and one study 19 was performed in Europe. Most studies (8/12) were retrospective cohort studies, and 11 studies were of high quality with a NOS score ≥ 7.…”

Section: Resultsmentioning

confidence: 99%

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Metformin and the risk of neurodegenerative diseases in patients with diabetes: A meta‐analysis of population‐based cohort studies

Zhang

Shi

et al. 2022

Diabet Med

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The association between metformin use and neurodegenerative disease (ND) onset remains controversial. In this systematic review and meta-analysis, we aimed to determine the relationship between metformin use and ND risk based on data from population-based cohort studies.Methods: Articles were systematically searched in PubMed, EMBASE and Cochrane Library databases. Pooled relative risks (RRs) with 95% CIs were obtained using a random-effects model. Subgroup analyses, sensitivity analyses and meta-regression were performed to identify the sources of heterogeneity and strengthen the results.Results: Twelve population-based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non-users) were eligible for inclusion in this meta-analysis. The pooled RR of NDs reached 0.77 (95% CI 0.67-0.88) when comparing metformin users with non-users. The effects were more prominent in long-term metformin users (≥4 years) (RR 0.29, 95% CI 0.13-0.44) and studies from Asian countries (RR 0.69, 95% CI 0.64-0.74). The effect estimates were stable when stratified by subtypes of NDs, study designs, and control definitions (p for interaction >0.05). Meta-regression did not identify the coefficients as the sources of heterogeneity (all p > 0.05). Conclusions:This systematic review and meta-analysis found that metformin use, especially long-term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high-quality randomized controlled trials are still needed to confirm this finding.

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Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: A systematic review and network meta‐analysis

Tian,

Jiang,

Wang

et al. 2023

Diabetes Metabolism Res

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We aimed to summarise current evidence on different antidiabetic drugs to delay cognitive impairment, including mild cognitive impairment, dementia, Alzheimer's disease (AD) and vascular dementia, among subjects with type 2 diabetes mellitus (T2DM). Medline, Cochrane and Embase databases were searched from inception to 31 July 2022. Two investigators independently reviewed and screened trials comparing antidiabetic drugs with no antidiabetic drugs, placebo, or other active antidiabetic drugs on cognitive outcomes in T2DM. Data were analysed using meta‐analysis and network meta‐analysis. Twenty‐seven studies met the inclusion criteria, including 3 randomised controlled trials, 19 cohort studies and 5 case‐control studies. Compared with non‐user, SGLT‐2i (OR 0.41 [95% CI 0.22–0.76]), GLP‐1RA (OR 0.34 [95% CI 0.14–0.85]), thiazolidinedione (OR 0.60 [95% CI 0.51–0.69]), and DPP‐4i (OR 0.78 [95% CI 0.61–0.99]) users had a decreased risk of dementia, whereas sulfonylurea (OR 1.43 [95% CI 1.11–1.82]) increased dementia risk. Network meta‐analysis showed that SGLT‐2i was most likely to rank best (SUCRA = 94.4%), GLP‐1 RA second best (SUCRA = 92.7%), thiazolidinedione third best (SUCRA = 74.7%) and DPP‐4i fourth best (SUCRA = 54.9%), while sulfonylurea second worst (SUCRA = 20.0%) for decreasing dementia outcomes, by synthesising evidence from direct and indirect comparisons of multiple intervention. Evidence suggests the effects of SGLT‐2i ≈ GLP‐1 RAs > thiazolidinedione > DPP‐4i for delaying cognitive impairment, dementia and AD outcomes, whereas sulfonylurea was associated with the highest risk. These findings provide evidence for evaluating the optional treatment for clinical practice.PROSPERO RegistrationRegistration no. CRD42022347280.

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Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort

Cited by 16 publications

References 31 publications

Association between non‐alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study

Association between non‐alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study

Metformin and the risk of neurodegenerative diseases in patients with diabetes: A meta‐analysis of population‐based cohort studies

Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: A systematic review and network meta‐analysis

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