Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies

Xu, Zhicheng; Zhang, Haidong; Wu, Chih-Wei; Zheng, Yuxiang; Jiang, Jingzhou

doi:10.3389/fcvm.2022.944902

Cited by 6 publications

(3 citation statements)

References 98 publications

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“…It has the potential to improve therapeutic outcomes in patients with ischemic heart disease and/or myocardial ischemia–reperfusion syndrome [ 53 ]. Research has reported that metformin has cardioprotective effects, including reducing myocardial infarct size, exerting positive effects on cardiac remodeling, preserving myocardium, and enhancing left ventricular functional activity [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl3 in Rat Models

Jabeen,

Rehman,

Akash

et al. 2023

Biomedicines

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Cardiovascular diseases (CVDs) and neurodegenerative disorders, such as diabetes mellitus and Alzheimer’s disease, share a common pathophysiological link involving insulin resistance (IR), inflammation, and hypertension. Aluminium chloride (AlCl3), a known neurotoxicant, has been associated with neurodegeneration, cognitive impairment, and various organ dysfunctions due to the production of reactive oxygen species (ROS) and oxidative stress. In this study, we aimed to investigate the potential protective effects of metformin and vitamin E against AlCl3-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl3-treated diseased group without any treatment, and three groups exposed to AlCl3 and subsequently administered with metformin (100 mg/kg/day) alone, vitamin E (150 mg/kg/day) orally alone, or a combination of metformin (100 mg/kg/day) and vitamin E (150 mg/kg/day) for 45 days. We analyzed serum biomarkers and histopathological changes in brain, heart, and pancreatic tissues using H&E and Masson’s trichrome staining and immunohistochemistry (IHC). Electrocardiogram (ECG) patterns were observed for all groups. The AlCl3-treated group showed elevated levels of inflammatory biomarkers, MDA, and disturbances in glycemic and lipid profiles, along with reduced insulin levels. However, treatment with the combination of metformin and vitamin E resulted in significantly reduced glucose, cholesterol, LDL, and TG levels, accompanied by increased insulin and HDL levels compared to the individual treatment groups. Histopathological analyses revealed that combination therapy preserved neuronal structures, muscle cell nuclei, and normal morphology in the brain, heart, and pancreatic tissues. IHC demonstrated reduced amyloid plaques and neurofibrillary tangles in the combination-treated group compared to the AlCl3-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl3-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl3-induced neuroinflammation and metabolic disturbances.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl3 in Rat Models

Jabeen,

Rehman,

Akash

et al. 2023

Biomedicines

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“…Another metaanalysis of nine observational studies pooling 34,504 T2D patients with HF receiving metformin versus controls (mostly sulfonylurea) reported a 20% reduction in mortality (HR: 0.80, (95% CI: 0.74-0.87)) and a 7% reduction in all-cause hospitalization (HR, 0.93; (95% CI: 0.89-0.98)) [67]. Of note, there was a non-significant 9% reduction in mortality in those with severe left ventricular dysfunction (HR, 0.91 (95% CI: 0.72-1.14)) [70]. A recent propensity score-matched observational study in 847 T2D patients with advanced HFrEF reported markedly lower B-type natriuretic peptide (BNP) levels, improved LVEF, and better event-free survival in metformin users than in controls irrespective of glycemic control [71].…”

Section: Metforminmentioning

confidence: 97%

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism

Hsu

Hsuan

Liao

et al. 2023

Life

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Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin–angiotensin II–aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

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“…In terms of other drugs, acarbose and miglitol exhibit excellent α-amylase and α-glucosidase inhibitory activities. However, they may result in abdominal distention, flatulence, vomiting, and diarrhea [4]. To solve these issues, more and more research evidence shows that natural foods from plants can also help control blood sugar and the fat content in cells.…”

Section: Introductionmentioning

confidence: 99%

Potential of Arabica Coffee Beans from Northern Thailand: Exploring Antidiabetic Metabolites through Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) Metabolomic Profiling across Diverse Postharvest Processing Techniques

Tantapakul,

Krobthong,

Jakkaew

et al. 2023

Foods

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Coffee, a widely consumed beverage worldwide, undergoes postharvest methods that influence its physicochemical characteristics, while roasting modulates its composition, affecting sensory attributes. This study investigates the impact of distinct postharvest methods (washed and natural) on the antidiabetic activities, including α-amylase and DPP4, as well as the phytochemical profiling of geological indicator (GI) coffee beans (Coffea arabica L.). The results indicate notable differences in antidiabetic activity and phytochemical profiles between washed and natural processing methods. Coffee beans processed naturally exhibit significant suppression of DPP4 and α-amylase activities (p-value < 0.01) compared to beans processed using the washed technique. TLC profiling using the ratios of the solvent systems of ethyl acetate/dichloromethane (DCM) and acetone/DCM as separation solvents reveals dominant spots for the washed technique. LC-MS/MS-based untargeted metabolomics analysis using principle component analysis (PCA) clearly segregates samples processed by the natural and washed techniques without any overlap region. A total of 1114 phytochemicals, including amino acids and short peptides, are annotated. The natural processing of coffee beans has been shown to yield a slightly higher content of chlorogenic acid (CGA) compared to the washed processing method. Our findings highlight the distinct bioactivities and phytochemical compositions of GI coffee beans processed using different techniques. This information can guide consumers in choosing coffee processing methods that offer potential benefits in terms of alternative treatment for diabetes.

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Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies

Cited by 6 publications

References 98 publications

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl3 in Rat Models

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl3 in Rat Models

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism

Potential of Arabica Coffee Beans from Northern Thailand: Exploring Antidiabetic Metabolites through Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) Metabolomic Profiling across Diverse Postharvest Processing Techniques

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