Metformin as adjuvant treatment in hepatitis C virus infections and associated complications

Landis, Dylan; Sutter, Alex; Khemka, Sachi; Songtanin, Busara; Nichols, Jacob; Nugent, Kenneth

doi:10.1016/j.amjms.2024.04.019

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…Metformin is the first-line therapy for T2D and most of the diabetes patients might have taken metformin. Metformin has been shown to reduce the risk of many bacterial and viral infections including zika virus ( 21 ), dengue virus ( 21 ), Hepatitis C virus ( 22 ), Streptococcus pneumoniae ( 23 ) and PTB ( 24 ). The use of metformin in many of the patients with T2D might have modified and attenuated the positive association between T2D and PTB.…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between type 2 diabetes and common respiratory system diseases: a two-sample Mendelian randomization analysis

Chen,

Zhang,

Sun

2024

Front. Med.

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BackgroundType 2 diabetes (T2D) frequently co-occurs with respiratory system diseases such as chronic obstructive pulmonary disease (COPD), bronchial asthma, lung cancer, interstitial lung disease, and pulmonary tuberculosis. Although a potential association is noted between these conditions, the available research is limited.ObjectiveTo investigate the causal relationship between patients with T2D and respiratory system diseases using two-sample Mendelian randomization analysis.MethodsCausal relationships were inferred using a two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies. We employed the variance inverse-weighted method as the primary analytical approach based on three key assumptions underlying MR analysis. To bolster the robustness and reliability of our results, we utilized MR Egger’s intercept test to detect potential pleiotropy, Cochran’s Q test to assess heterogeneity, funnel plots to visualize potential bias, and “leave-one-out” sensitivity analysis to ensure that our findings were not unduly influenced by any single genetic variant.ResultThe inverse variance weighted (IVW) analysis indicated a causal relationship between T2D and COPD [Odds Ratio (OR) = 0.87; 95% Confidence Interval (CI) = 0.82–0.96; p < 0.05]. No significant heterogeneity or pleiotropy were observed through their respective tests (p > 0.05), and the statistical power calculations indicated that the results were reliable. The IVW analysis showed a negative causal relationship between T2D and bronchial asthma [OR = 0.85; 95% CI = 0.81–0.89; p < 0.05]. However, the IVW under the random-effects model indicated heterogeneity (p < 0.05), suggesting instability in the results and requiring cautious interpretation. The study found a positive causal relationship between T2D and pulmonary tuberculosis (OR = 1.24, 95% CI = 1.05–1.45, p < 0.05). However, they exhibited pleiotropy (p < 0.05), indicating their instability. No correlation between T2D and interstitial lung disease or lung cancer was observed.ConclusionT2D is negatively associated with COPD, suggesting that T2D may reduce the risk of developing COPD. A negative causal relationship between T2D and bronchial asthma has been observed, but the results exhibit heterogeneity. There is a positive causal relationship between T2D and pulmonary tuberculosis, yet the findings suggest the presence of pleiotropy. No significant causal relationship between T2D and lung cancer or interstitial lung disease was observed.

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Section: Discussionmentioning

confidence: 99%

Causal relationship between type 2 diabetes and common respiratory system diseases: a two-sample Mendelian randomization analysis

Chen,

Zhang,

Sun

2024

Front. Med.

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Klotho Deficiency in Severe COVID-19: A Unifying Hypothesis

Campos-Obando,

Zillikens,

Macaya

2024

COVID

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COVID-19 is characterized by a striking similarity to premature aging. Its clinical manifestations range from asymptomatic to critical illness. No single central agent has been demonstrated so far. We present Klotho, an antiaging protein, as a key factor in COVID-19 pathophysiology. There is epidemiological evidence that both acute and chronic uses of Klotho agonists have a beneficial effect in reducing COVID-19 severity and mortality. A review of the PubMed epidemiological, clinical, and mechanistic evidence supports a role for Klotho deficit as a central determinant of severe COVID-19. Clinical data support the idea that chronic use of Klotho agonists protects against severe COVID-19 and that its acute use may be beneficial. We propose a unifying hypothesis that low Klotho levels play a key role in severe COVID-19, while increasing Klotho levels can have a beneficial effect through the prevention of acute kidney injury (AKI) and potential antiviral effects. Further research is needed.

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Metformin in Antiviral Therapy: Evidence and Perspectives

Halabitska,

Petakh,

Lushchak

et al. 2024

Viruses

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Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV. Furthermore, metformin reduces oxidative stress and reactive oxygen species (ROS), which are critical for replicating arboviruses such as Zika and dengue. The drug also regulates immune responses, cellular differentiation, and inflammation, disrupting the life cycle of HPV and potentially other viruses. These diverse mechanisms suppress viral replication, enhance immune system functionality, and contribute to better clinical outcomes. This multifaceted approach highlights metformin’s potential as an adjunctive therapy in treating a wide range of viral infections.

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Metformin as adjuvant treatment in hepatitis C virus infections and associated complications

Cited by 3 publications

References 49 publications

Causal relationship between type 2 diabetes and common respiratory system diseases: a two-sample Mendelian randomization analysis

Causal relationship between type 2 diabetes and common respiratory system diseases: a two-sample Mendelian randomization analysis

Klotho Deficiency in Severe COVID-19: A Unifying Hypothesis

Metformin in Antiviral Therapy: Evidence and Perspectives

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