Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: a systematic review

Geng, Yifei; Wang, Zhen; Xu, Xiaoyu; Sun, Xueying; Xi, Dong; Luo, Yun; Sun, Xiangrong

doi:10.1016/j.trsl.2023.08.001

Cited by 3 publications

(2 citation statements)

References 222 publications

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“…Yet, only a few observational studies have assessed the prevalence of such side effects in the real world. Metformin has an impact on gut microbiota, 49 and may interact with various bowel effectors, including serotoninergic balance and bile acids; it also modifies ghrelin secretion after glucose loading and stimulates GLP‐1 secretion. The extended‐release (ER) pharmacological formulation, allowing the release of the active component of the drug in the upper gastrointestinal tract, has been shown to improve its tolerability 50,51 .…”

Section: Tolerability and Dose‐dependent Side Effectsmentioning

confidence: 99%

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

Solini,

Tricò

2024

Diabetes Obesity Metabolism

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Over the past two decades, diabetes pharmacopoeia has flourished, with new drugs that, on top of their glucose‐lowering efficacy, have been shown to protect the heart and the kidney. Despite these new opportunities, metformin retains a pivotal role among glucose‐lowering agents. As one of the few available insulin sensitizers, metformin is an effective, safe, and overall well‐tolerated drug backed by over 60 years of clinical experience, including evidence for potential benefits beyond glucose reduction across different ages, sexes, genetic backgrounds, geographical areas, and stages of disease. Although there is some discussion of whether metformin offers the most effective front‐line option in newly diagnosed type 2 diabetes (T2D), it remains a natural companion to all other glucose‐lowering agents. Furthermore, metformin comes at a very low cost and, as such, it has extremely high cost‐effectiveness, particularly given the serious economic burden associated with diabetes complications. This financial advantage is particularly relevant in resource‐constrained healthcare systems, where the affordability of metformin may be instrumental in implementing an effective treatment in an evergrowing number of individuals. We present here compelling real‐world evidence in support of the clinical efficacy and cost‐effectiveness of metformin across different patient populations, highlighting areas where more population‐based studies are needed to further incorporate and consolidate its use in the pharmacological management of T2D.

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Section: Tolerability and Dose‐dependent Side Effectsmentioning

confidence: 99%

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

Solini,

Tricò

2024

Diabetes Obesity Metabolism

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“…Both experimental and clinical data indicated that metformin, the primary oral antihyperglycemic agent with pharmacological adenosine 5’ monophosphate-activated protein kinase (AMPK) activation, could improve the cardiometabolic status in populations with obesity, diabetes, or psychiatric disorders [ 8 ]. This improvement was attributed to mechanisms including oxidative stress inhibition and redox rebalance [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study

Li,

Liu,

et al. 2024

BMC Med

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Background In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. Methods A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants’ levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. Results Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44–0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28–0.59), stroke (OR, 0.44; 95% CI, 0.26–0.74), hypertension (OR, 0.27; 95% CI, 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21–0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. Conclusions In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

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Pump‐Less, Recirculating Organ‐on‐Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver

Aizenshtadt,

Wang,

Abadpour

et al. 2024

Adv Healthcare Materials

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Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction‐associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump‐less recirculating Organ‐on‐Chip (dual‐rOoC) platform that combines human pluripotent stem cell (sc)‐derived sc‐liver and sc‐islet organoids is presented. The platform reproduces key aspects of the metabolic cross‐talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc‐islet and sc‐liver organoids while preserving a reduced release of pro‐inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc‐liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc‐islets produce pro‐inflammatory cytokines on‐chip. Finally, the platform reproduces known effects of anti‐diabetic drugs on‐chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on‐chip, as well as for testing potential therapeutic interventions.This article is protected by copyright. All rights reserved

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Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: a systematic review

Cited by 3 publications

References 222 publications

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study

Pump‐Less, Recirculating Organ‐on‐Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver

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