Table 2 Study characteristics
From: Metformin mitigates dementia risk among individuals with type 2 diabetes
S/N | Study Name | Author names | Study design | Sample size | Positive Outcome | Negative Outcome |
|---|---|---|---|---|---|---|
1. | Dementia Risk in Type 2 Diabetes Patients: Acarbose Use and Its Joint Effects with Metformin and Pioglitazone | Chin-Hsiao Tseng 2019 [20] | population-based retrospective cohort study | 446,105 | -Reduced risk of dementia associated with acarbose is observed in the female sex and in non-users of metformin -Users of all three drugs (acarbose, metformin, and pioglitazone) have the lowest risk of dementia | |
2. | Long-Term Metformin Usage and Cognitive Function among Older Adults with Diabetes | Tze Pin Ng et al. 2014 [15] | population-based 4-year prospective study | 365 | -Long-term treatment with metformin may reduce the risk of cognitive decline in individuals with diabetes | No significant interactive effects of metformin use with APOE-4, depression, or fasting glucose level were observed |
3. | Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort | Yonghwan Kim et al. 2020 [19] | Longitudinal study | 514,794 | -The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73–1.28), 0.77 (0.58–1.01), 0.48 (0.35–0.67), and 0.98 (0.84– 1.15), respectively, in men, respectively, and 0.90 (0.65–0.98), 0.61 (0.50–0.76), 0.46 (0.36– 0.58), and 0.92 (0.81–1.04), respectively, in women, after full adjustment of confounding variables -Metformin use in an elderly population with DM reduced dementia risk in a dose–response manner | |
4. | Metformin vs sulfonylurea use and risk of dementia in US veterans aged $65 years with diabetes | Ariela R. Orkaby et al. 2017 [13] | retrospective cohort study | 432,922 | -metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans,75 years of age - A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values $7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99) | |
5. | Incidence of Dementia is Increased in Type 2 Diabetes and Reduced by the Use of Sulfonylureas and Metformin | Chih-Cheng Hsu et al. 2011 [11] | Representative cohort study | 127,209 | sulfonylureas and metformin may decrease the risk of dementia; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years | |
6. | Metformin and the Risk of Dementia in Type 2 Diabetes Patients | Chin-Hsiao Tseng 2019 [20] | retrospective cohort study | 423,949 | metformin use is associated with a reduced dementia risk | |
7. | Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study | Katherine Samaras et al. 2020 [14] | prospective observational study | 1,037 | Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk | |
8. | Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus | Yi-Chun Kuan et al. 2017 [28] | Cohort study | Taiwan’s National Health Insurance Research Database > 50yrs 4651 metformin cohorts | -The metformin cohort had an increased risk of all-cause dementia (HR: 1.66, 95% CI = 1.35–2.04) - metformin exposure increased the risk of Alzheimer’s disease (HR: 2.13, 95% CI = 1.20–3.79) and vascular dementia (HR: 2.30, 95% CI = 1.25–4.22) - Long-term metformin exposure in patients with T2DM may lead to the development of NDs, including dementia and PD | |
9. | Metformin and Sulfonylurea Use and Risk of Incident Dementia | cohort studies | 75,187 VHA patients 10,866 KPW patients > 50yrs | Metformin use is associated with a modestly lower risk of incident dementia | ||
10. | The Correlation between Metformin Use and Incident Dementia in Patients with New-Onset Diabetes Mellitus: A Population-Based Study | Kuang-Hua Huang et al. 2023 [16] | population-based study | 736,473 | Patients with a low intensity of metformin use had a lower risk of dementia | higher doses of metformin with higher intensity exhibited no protective role in dementia |
11. | The Association between Metformin Use and Risk of Developing Severe Dementia among AD Patients with Type 2 Diabetes | Ying xue et al. 2023 [29] | a propensity score-matched cohort | 1306 | metformin usage is not significantly associated with a decreased risk of severe dementia | |
12. | Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial | Luchsinger, José A et al. 2016 [17] | Pilot Randomized Placebo Controlled Clinical Trial | 80 55-90yrs | After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group (9.7 ± 8.5 versus 5.3 ± 8.5; p = 0.02) | 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms |
13. | Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study | José A. Luchsinger et al. 2017 [30] | observational study | 2,280 | -There were no differences in cognition across intervention arms -Type 2 diabetes was not related to cognition, but higher glycated hemoglobin at year 8 was related to worse cognition after confounder adjustment -Cumulative metformin exposure was not related to cognition | |
14. | Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial | Kwang-Pil Ko et al. 2015 [22] | phase II randomized, double-blind, placebo-controlled trial | 105 | Metformin 1000 mg treatment had a favorable effect on controlling glucose and HbA1C levels in obese non-diabetic breast cancer patients, indicating prognostic importance | |
15. | Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case–control study | Ida Kim Wium-Andersen et al. 2019 [10] | nested case–control study | 176 250 patients | Use of metformin, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multiple adjustments (ORs of 0.94 (95% confidence interval (CI): 0.89–0.99), 0.80 (95% CI 0.74–0.88), 0.58 (95% CI: 0.50–0.67), and 0.58 (95% CI: 0.42–0.81), respectively | |
16. | Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients | retrospective cohort study | 73,761 > 50yrs | - metformin vs sulfonylurea use was associated with a significantly lower risk of dementia in African American patients (hazard ratio [HR] = 0.73; 95% CI, 0.6–0.89) but not white patients (HR = 0.96; 95% CI, 0.9–1.03) - Among those aged 65 to 74 years, metformin was significantly associated with lower risk of dementia in both races - Metformin was not associated with dementia in patients aged ≥ 75 years | ||
17. | Comparative effect of metformin versus sulfonylureas with dementia and Parkinson’s disease risk in US patients over 50 with type 2 diabetes mellitus | Danielle Newby et al 2022 [24] | comparator study | 96 140 metformin users 16 451 sulfonylurea users | Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI | |
18. | Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial | Jolien de Jager et al. 2010 [25] | Multicentre randomised placebo controlled trial | 390 | Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations | |
19. | Collocation of metformin and dipeptidyl peptidase-4 inhibitor is associated with increased risk of diabetes-related vascular dementia: A single hospital study in Northern Taiwan | I-Shiang Tzeng et al. 2023 [26] | observational and data-driven studies | 67,281 | the combination therapy of metformin and DPP-4 inhibitor may increase the risk of dementia compared with that in the control group (adjusted hazard ratio, 1.11; 95% confidence interval, 1.06–1.15; p ≤ 0.001) | |
20. | Extended-release metformin improves cognitive impairment in frail older women with hypertension and diabetes: preliminary results from the LEOPARDESS Study | Mone et al., 2023 [27] | Randomised Control Trial | 145 | Significant different cognitive performance compared to baseline in the group of frail women treated with extended-release metformin | |
21. | Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway | Zhou et al., 2021 [31] | Preclinical Study | Metformin administration alleviates the LPS-induced memory dysfunction and improves synaptic plasticity | ||
22. | Metformin restores cognitive dysfunction and histopathological deficits in an animal model of sporadic Alzheimer's disease | Rabieipoor et al., 2023 [32] | Preclinical Study | Metformin decreased inflammatory cells and reactive astrocytes as well as the dying neurons in the hippocampus region and the cortex in SAD, and improved the cognitive performance | ||
23. | Effect of Metformin on Short-Term High-Fat Diet-Induced Weight Gain and Anxiety-Like Behavior and the Gut Microbiota | Ji et al., 2019 [33] | Preclinical Model | For a short-term 3-week co-treatment, metformin alleviated the HFD-induced increase in body weight, the increase in adipocyte size and furthermore, the anxiety-like behavior |