Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis

Ping, Fan; Jiang, Ning; Li, Yuxiu

doi:10.1136/bmjdrc-2020-001370

Cited by 51 publications

(53 citation statements)

References 43 publications

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“…Overall, we also found a lack of association between metformin use and PD, but after excluding data from one study (35), the results showed a significant association. In a previous meta-analysis, Ping et al (11) reported a lack of association between metformin use and the general risk of neurodegenerative diseases, but an increased PD risk in a subgroup analysis of three studies. These paradoxical results between studies can be attributed to inter-study heterogeneity in the populations, drug dosages and duration, classes of drugs, follow-up lengths, and adjusted factors.…”

Section: Discussionmentioning

confidence: 98%

“…Among the strengths of our study, this is the first comprehensive review assessing the impact of different DM medications on the PD risk. Unlike prior reviews (11)(12)(13), ours includes a detailed analysis for every oral DM drug in literature. We obtained data from many new studies and therefore our analysis presents the most updated evidence on the subject.…”

Section: Discussionmentioning

confidence: 99%

“…Over the last decade, much research has been conducted on the influence of specific DM drugs and the PD risk in patients with DM. Systematic reviews have pooled the evidence for single drugs like metformin or glitazones (GTZ) based on data from only 3-4 studies each (11)(12)(13). The evidence for other DM medications like sulfonylureas, dipeptidyl peptidase-4 inhibitors (DDP4i), and glucagon-like peptide-1 receptor agonists (GLP1a) has not been synthesized.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

Qin

Xia

et al. 2021

Front. Neurol.

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Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM.Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a).Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I2, 0%; p = 0.02).Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

Qin

Xia

et al. 2021

Front. Neurol.

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“…A meta-analysis that includes 285,966 participants further finds no significant effect on the incidence of all the subtypes of neurodegenerative diseases with metformin exposure. Instead, metformin monotherapy is associated with a significantly increased risk of PD incidence (Ping et al, 2020).…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Metformin: A Novel Weapon Against Inflammation

Bai

Chen

2021

Front. Pharmacol.

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It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin’s inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin’s anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin’s utility in this clinical setting.

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“…The current pharmacological approaches for diabetes mellitus and neurodegenerative diseases are unable to reverse diseases and focus mainly on managing symptoms by slowing progression. Furthermore, most modern drugs cause several adverse effects exacerbating the medical conditions following prolonged treatment [31]. However, recent advancements in proteomics have made it possible to obtain high quality peptide-drug conjugates though a variety of coupling techniques.…”

Section: Small Bioactive Compoundsmentioning

confidence: 99%

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

2022

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It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in ameliorating type 2 diabetes mellitus symptoms. Furthermore, both diabetes and neurodegenerative conditions, such as AD, are characterized by chronic inflammatory responses accompanied by the presence of dysregulated inflammatory biomarkers. This review presents current evidence describing the role of various small bioactive molecules known to ameliorate amyloidosis and subsequent effects in prevention and development of diabetes and AD. It also highlights the potential efficacy of peptide–drug conjugates capable of targeting intracellular targets.

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Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis

Cited by 51 publications

References 43 publications

Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

Metformin: A Novel Weapon Against Inflammation

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

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