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Archives of Pharmacal Research May 2023Metformin has been used clinically for more than 60 years. As time goes by, more and more miraculous effects of metformin beyond the clinic have been discovered and... (Review)
Review
Metformin has been used clinically for more than 60 years. As time goes by, more and more miraculous effects of metformin beyond the clinic have been discovered and discussed. In addition to the clinically approved hypoglycemic effect, it also has a positive metabolic regulation effect on the human body that cannot be ignored. Such as anti-cancer, anti-aging, brain repair, cardiovascular protection, gastrointestinal regulation, hair growth and inhibition of thyroid nodules, and other nonclinical effects. Metformin affects almost the entire body in the situation taking it over a long period, and the preventive effects of metformin in addition to treating diabetes are also beginning to be recommended in some guidelines. This review is mainly composed of four parts: the development history of metformin, the progress of clinical efficacy, the nonclinical efficacy of metformin, and the consideration and prospect of its application.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Neoplasms; Aging
PubMed: 36964307
DOI: 10.1007/s12272-023-01445-2 -
Expert Review of Endocrinology &... Mar 2019Combining antihyperglycemic agents in order to rapidly and safely achieve the best possible glycemic control is the standard of care today for the management of type 2... (Review)
Review
Combining antihyperglycemic agents in order to rapidly and safely achieve the best possible glycemic control is the standard of care today for the management of type 2 diabetes. Agents should ideally have mechanisms of actions that are complementary and that improve glycemic control without unacceptable gain in body weight or hypoglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. This review summarizes key characteristics of ertugliflozin and metformin, as well as the efficacy and safety results of co-administration of these agents in the ertugliflozin clinical development program. This information comes from the ertugliflozin/metformin prescribing information as well as published clinical trials obtained through a PubMed search. Expert commentary: SGLT-2 inhibitors are an important class of antihyperglycemic agents that are efficacious as monotherapy and in combination with other antihyperglycemic agents. Given their favorable effects on glycemia control as well as 'extra-glycemic' parameters such as body weight and blood pressure, they are ideal agents for appropriate patients with type 2 diabetes. The fixed-dose combination of ertugliflozin with metformin is an effective combination that is conveniently administered and may improve medication adherence and persistence.
Topics: Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypoglycemic Agents; Metformin; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Treatment Outcome
PubMed: 30724637
DOI: 10.1080/17446651.2019.1571908 -
Diabetes Research and Clinical Practice Jan 2020Metformin is the most widely used glucose lowering drug worldwide in the treatment of patients with type 2 diabetes, since we have experience with this drug for more... (Review)
Review
Metformin is the most widely used glucose lowering drug worldwide in the treatment of patients with type 2 diabetes, since we have experience with this drug for more than 60 years about the efficacy and safety. Metformin is very effective in HbA1c lowering associated with some weight loss, but does not increase risk for hypoglycemia. At the moment all guidelines in the world recommend to use metformin in monotherapy in patients with newly diagnosed diabetes or in combination with other antidiabetic drugs with documented CV (and renal) benefit in cardiovascular outcome trials (CVOT). Although a randomized placebo controlled CVOT with metformin is lacking, many observational studies in patients with coronary heart disease, heart failure and chronic kidney disease have demonstrated consistent beneficial effects. A recent metanalysis of 26 observational studies including 815 839 patients showed that metformin use was associated with a significantly lower rate of all-cause mortality (HR: 0.74; 95% CI: 0.68-0.81). Whether this very consistent reduction of all-cause mortality is related to the incidence/outcome of several cancers has still to be investigated. In the future early combination therapy of metformin e.g. with SGLT-2 inhibitors should be more often used.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Middle Aged
PubMed: 31778746
DOI: 10.1016/j.diabres.2019.107946 -
American Journal of Physiology.... Oct 2023The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin...
The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre-diabetes and type 2 diabetes (T2D). Eight T2D adults (60 ± 4 yr) with overweight/obesity (32 ± 4 kg·m) under chronic metformin treatment (9 ± 6 yr; 1281 ± 524 mg·day) underwent four trials; ) taking their habitual metformin treatment (MET), ) substituting during 96 h their metformin medication by placebo (PLAC), ) placebo combined with 50 min bout of high-intensity interval exercise (PLAC + EX), and ) metformin combined with exercise (MET + EX). Plasma glucose kinetics using stable isotopes (6,6-H and [U-C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDA and OGIS). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET + EX lower than PLAC and PLAC + EX, respectively; = 0.023). MET + EX increased MATSUDA above PLAC (4.8 ± 1.4 vs. 3.3 ± 1.0, respectively; = 0.018) and OGIS above PLAC (358 ± 52 vs. 306 ± 46 mL·min·m, respectively; = 0.006). Metformin decreased the plasma appearance of the ingested glucose (R OGTT; MET vs. PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg·min; = 0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre-diabetes and type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise. Metformin is the most prescribed oral antidiabetic medicine in the world but its mechanism of action and its interactions with exercise are not fully understood. Our stable isotope tracer data suggested that metformin reduces the rates of oral glucose entering the circulation (gut-liver effect). Exercise, in turn, tended to reduce postprandial insulin blood levels potentiating metformin improvements in insulin sensitivity. Thus, exercise potentiates metformin improvements in glycemic control and should be advised to metformin users.
Topics: Adult; Humans; Metformin; Glucose; Prediabetic State; Insulin Resistance; Diabetes Mellitus, Type 2; Kinetics; Blood Glucose; Insulin
PubMed: 37584610
DOI: 10.1152/ajpendo.00118.2023 -
Current Problems in Cancer Aug 2023Metformin is an ancient drug for the treatment of type 2 diabetes, and many studies now suggested that metformin can be used as an adjuvant drug in the treatment of many... (Review)
Review
Metformin is an ancient drug for the treatment of type 2 diabetes, and many studies now suggested that metformin can be used as an adjuvant drug in the treatment of many types of tumors. The mechanism of action of metformin for tumor treatment mainly involves: 1. activation of AMPK signaling pathway 2. inhibition of DNA damage repair in tumor cells 3. downregulation of IGF-1 expression 4. inhibition of chemoresistance and enhancement of chemotherapy sensitivity in tumor cells 5. enhancement of antitumor immunity 6. inhibition of oxidative phosphorylation (OXPHOS). Metformin also plays an important role in the treatment of hematologic tumors, especially in leukemia, lymphoma, and multiple myeloma (MM). The combination of metformin and chemotherapy enhances the efficacy of chemotherapy, and metformin reduces the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. The purpose of this review is to summarize the anticancer mechanism of metformin and the role and mechanism of action of metformin in hematologic tumors. We mainly summarize the studies related to metformin in hematologic tumors, including cellular experiments and animal experiments, as well as controlled clinical studies and clinical trials. In addition, we also focus on the possible side effects of metformin. Although a large number of preclinical and clinical studies have been performed and the role of metformin in preventing the progression of MGUS to MM has been demonstrated, metformin has not been approved for the treatment of hematologic tumors, which is related to the adverse effects of its high-dose application. Low-dose metformin reduces adverse effects and has been shown to alter the tumor microenvironment and enhance antitumor immune response, which is one of the main directions for future research.
Topics: Animals; Humans; Metformin; Diabetes Mellitus, Type 2; Drug Repositioning; Multiple Myeloma; Hematologic Neoplasms; Tumor Microenvironment
PubMed: 37364455
DOI: 10.1016/j.currproblcancer.2023.100972 -
Current Osteoporosis Reports Dec 2023Metformin is an anti-glycemic agent, which is widely prescribed to diabetes patients. Although its alleged role on bone strength has been reported for some time, this... (Review)
Review
PURPOSE OF REVIEW
Metformin is an anti-glycemic agent, which is widely prescribed to diabetes patients. Although its alleged role on bone strength has been reported for some time, this review focuses primarily on the recent mechanistical insights of metformin on osteocytes, osteoblasts, and osteoclasts.
RECENT FINDINGS
Overall, metformin contributed to steering anabolic activity in osteocytes. It caused lower expression in osteocytes of the negative regulators of bone formation sclerostin and DKK1. Likewise, the osteoclastogenesis function of osteoblasts was also skewed towards lower RANKL and higher OPG expressions. Osteoblast lineage cells generally responded to metformin by activating bone formation parameters, such as alkaline phosphatase activity, higher expression of anabolic members of the Wnt pathway, transcription factor Runx2, bone matrix protein proteins, and subsequent mineralization. Metformin affected osteoclast formation and activity in a negative way, reducing the number of multinucleated cells in association with lower expression of typical osteoclast markers and with inhibited resorption. A common denominator studied in all three cell types is its beneficial effect on activating phosphorylated AMP kinase (AMPK) which is associated with the coordination of energy metabolism. Metformin differentially affects bone cells, shifting the balance to more bone formation. Although metformin is a drug prescribed for diabetic patients, the overall bone anabolic effects on osteocytes and osteoblasts and the anti-catabolic effect on osteoclast suggest that metformin could be seen as a promising drug in the bone field.
Topics: Humans; Osteoclasts; Osteocytes; Metformin; Osteoblasts; Bone and Bones; RANK Ligand; Cell Differentiation
PubMed: 37796390
DOI: 10.1007/s11914-023-00828-0 -
MMW Fortschritte Der Medizin Jun 2024
Review
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Drug Therapy, Combination
PubMed: 38806900
DOI: 10.1007/s15006-024-4003-3 -
Oncology 2016Several clinical studies demonstrated that diabetic patients treated with metformin were less likely to develop vascular complications, independent of glycemic control.... (Review)
Review
Several clinical studies demonstrated that diabetic patients treated with metformin were less likely to develop vascular complications, independent of glycemic control. It was also demonstrated that the large variety of metformin's vascular actions can be seen in nondiabetic conditions. Metformin has an interesting potential to treat vascular dysfunction and tumor angiogenesis in conditions beyond diabetes. Since metformin's use in cancer as a single antiangiogenic agent appears to be a therapeutic disappointment, the use of the drug as part of combination anticancer modality represents a therapeutic challenge. The normalization of vascular dysfunction as a new therapeutic strategy may provide better delivery of conventional anticancer agents to the tumor and disrupted tumor environment. In this review, we will outline the available information from the literature regarding metformin and tumor angiogenesis and suggest eventual experimental and clinical approaches.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Humans; Metformin; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 27487294
DOI: 10.1159/000448175 -
Biomaterials Apr 2023Physiological barriers and immunosuppressive microenvironments of solid tumors present considerable hurdles to Chimeric antigen receptor T (CAR-T) cell therapy. Herein,...
Physiological barriers and immunosuppressive microenvironments of solid tumors present considerable hurdles to Chimeric antigen receptor T (CAR-T) cell therapy. Herein, we discovered that metformin, a prescribed drug for type 2 diabetes, could up-regulate the oxidative phosphorylation of CAR-T cells, increase their energy metabolism, and further promote their proliferation. Inspired by this finding, we designed a hydrogel scaffold to co-deliver metformin and CAR-T cells by adding CAR-T cells into a lyophilized alginate hydrogel containing metformin. The obtained hydrogel scaffold after being implanted into the tumor resection cavity could act as a cell reservoir to sustainably release both CAR-T cells and metformin. While the released metformin could suppress oxidative and glycolytic metabolism of cancer cells and lead to decreased tumor hypoxia, CAR-T cells would respond to metformin by markedly up-regulating oxidative metabolism and adopting a long-lived, highly activated phenotype, contributing to elevated antitumor responses. As demonstrated in several post-surgical tumor models, the proliferation and tumor-infiltration of CAR-T cells were significantly enhanced and the treatment efficacy of CAR-T cells was augmented, against both local tumors and distant abscopal tumors, while showing reduced systemic immune-related adverse effects. Our work presents a new strategy to achieve effective yet safe CAR-T therapy against solid tumors using a cell-delivery scaffold based on clinically validated drugs and biomaterials.
Topics: Humans; Receptors, Chimeric Antigen; Metformin; Diabetes Mellitus, Type 2; Hydrogels; T-Lymphocytes; Neoplasms; Immunotherapy, Adoptive; Tumor Microenvironment
PubMed: 36827893
DOI: 10.1016/j.biomaterials.2023.122052 -
Polski Merkuriusz Lekarski : Organ... Feb 2022Diabetes as chronic civilization disease, very often occurs together with health disorders. One of the basic pharmaceuticals commonly used in her therapy is metformin.... (Review)
Review
Diabetes as chronic civilization disease, very often occurs together with health disorders. One of the basic pharmaceuticals commonly used in her therapy is metformin. Many other positive effects, not related to diabetes, have been observed in tatients treated with metformin for a long time. These are: positive changes in diagnostiic parameters, protection against cancer development, less frequent occurrence of other pathologies and diseases, increased sensitivity to selected drugs (e.g. cytostatics), delayed aging processes of organism. In addition to the molecular changes resulting in a hypoglycemic effect, the most common modifications of gene expression have been described, indicated as the basis for the anti-aging, anti-atherosclerotic and anticancer effects of this drug and its effect on melanogenesis or the nervous system. The results presented in the study are very promising, but most of them relate to experiments carried out in cell cultures or animals. The possibility of obtaining similar effects in humans requires much more research.
Topics: Aging; Animals; Diabetes Mellitus; Female; Hypoglycemic Agents; Metformin; Neoplasms
PubMed: 35278303
DOI: No ID Found