Metformin for diabetes prevention: update of the evidence base

Hostalek, Ulrike; Campbell, Ian W

doi:10.1080/03007995.2021.1955667

Cited by 34 publications

(35 citation statements)

References 109 publications

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“…We found that MET has a neuroprotective effect in vivo and in vitro by inhibiting nerve cell pyroptosis and inflammation. MET is a biguanide hypoglycaemic agent normally used to treat type 2 diabetes [ 6 ]. A large number of studies have made clear that MET puts power into neuroprotective effects on some CNS diseases and neurodegenerative diseases [ 7 , 8 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Metformin (MET) is a hypoglycemic drug commonly utilized in the treatment of type 2 diabetes [ 5 ], as it gets more out of hyperglycaemia without causing endogenous insulin secretion or hypoglycaemia [ 6 ]. In addition to its role in lowering blood glucose levels, MET has been shown to be a potent candidate for a variety of central nervous system (CNS) infections, including Parkinson's sickness, Alzheimer's illness, and ischemic cerebrum damage [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Yuan¹,

Fan

Guo³

et al. 2022

Analytical Cellular Pathology

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Spinal cord injury (SCI) is an extreme neurological impairment with few effective drug treatments. Pyroptosis is a recently found and proven type of programmed cell death that is characterized by a reliance on inflammatory caspases and the release of a large number of proinflammatory chemicals. Pyroptosis differs from other cell death mechanisms such as apoptosis and necrosis in terms of morphological traits, incidence, and regulatory mechanism. Pyroptosis is widely involved in the occurrence and development of SCI. In-depth research on pyroptosis will help researchers better understand its involvement in the onset, progression, and prognosis of SCI, as well as provide new therapeutic prevention and treatment options. Herein, we investigated the role of AMPK-mediated activation of the NLRP3 inflammasome in the neuroprotection of MET-regulated pyroptosis. We found that MET treatment reduced NLRP3 inflammasome activation by activating phosphorylated AMPK and reduced proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release. At the same time, MET improved motor function recovery in rats after SCI by reducing motor neuron loss in the anterior horn of the spinal cord. Taken together, our study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AMPK pathway increase, hence decreasing NLRP3 inflammasome activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Yuan¹,

Fan

Guo³

et al. 2022

Analytical Cellular Pathology

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“…Although diabetes incidence reduced in both placebo and metformin arms — from 11.0 cases and 7.8 cases per 100 person‐years respectively during the trial to 5.6 and 4.9 cases per 100 person‐years (comparable to the lifestyle intervention group) after trial completion — the difference in cumulative incidence persisted between placebo and metformin, which the research team attributed to possible “exhaustion of susceptibles” 21 . This suggestion is supported by DPP findings of greatest impact in younger, overweight individuals, which is highly pertinent considering the profile of patients with serious mental illness when they are starting antipsychotic therapy 18 . Limited evidence exploring the potential of combining metformin therapy and lifestyle modification has not demonstrated a significantly reduced rate of diabetes onset compared with either intervention individually 22 …”

Section: Metformin To Prevent Diabetesmentioning

confidence: 97%

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Namara

Alzubaidi

Murray

et al. 2022

Medical Journal of Australia

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Summary Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP‐1RAs suggest that these medications are associated with a high prevalence of mild–moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP‐1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic‐induced weight gain is worth considering in Australia. This would bring us into line with other countries.

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“…Metformin is often used off-label in the management of prediabetes and polycystic ovary syndrome ( Hostalek et al, 2015 ; Guan Y. et al, 2020 ; Hostalek and Campbell, 2021 ). Database analyses to specifically assess the effect of metformin on the severity of Covid-19 infections in these conditions have not been reported.…”

Section: Metformin and Covid-19mentioning

confidence: 99%

Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin

Bailey

Gwilt

2022

Front. Pharmacol.

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Objectives: Pre-existing or new diabetes confers an adverse prognosis in people with Covid-19. We reviewed the clinical literature on clinical outcomes in metformin-treated subjects presenting with Covid-19.Methods: Structured PubMed search: metformin AND [covid (ti) OR covid-19 (ti) OR covid19 (ti) OR coronavirus (ti) OR SARS-Cov2 (ti)], supplemented with another PubMed search: “diabetes AND [covid OR covid-19 OR covid19 OR coronavirus (i) OR SARS-Cov2 (ti)]” (limited to “Clinical Study”, “Clinical Trial”, “Controlled Clinical Trial”, “Meta-Analysis”, “Observational Study”, “Randomized Controlled Trial”, “Systematic Review”).Results: The effects of metformin on the clinical course of Covid-19 were evaluated in retrospective analyses: most noted improved clinical outcomes amongst type 2 diabetes patients treated with metformin at the time of hospitalisation with Covid-19 infection. These outcomes include reduced admission into intensive care and reduced mortality in subgroups with versus without metformin treatment.Conclusion: The pleiotropic actions of metformin associated with lower background cardiovascular risk may mediate some of these effects, for example reductions of insulin resistance, systemic inflammation and hypercoagulability. Modulation by metformin of the cell-surface ACE2 protein (a key binding target for SARS-CoV 2 spike protein) via the AMP kinase pathway may be involved. While pre-existing metformin treatment offers potentially beneficial effects and can be continued when Covid-19 infection is not severe, reports of increased acidosis and lactic acidosis in patients with more severe Covid-19 disease remind that metformin should be withdrawn in patients with hypoxaemia or acute renal disease. Prospective study of the clinical and metabolic effects of metformin in Covid-19 is warranted.

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Metformin for diabetes prevention: update of the evidence base

Cited by 34 publications

References 109 publications

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin

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