Metformin: Past, Present, and Future

Current Diabetes Reports, Journal Year: 2024, Volume and Issue: 24(6), P. 119 - 130

Published: April 3, 2024

Language: Английский

---

Metformin: Therapeutic profile in the treatment of type 2 diabetes

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(S3), P. 3 - 19

Published: May 24, 2024

Metformin (dimethyl-biguanide) can claim its origins in the use of Galega officinalis as a plant treatment for symptoms ascribed to diabetes. Since first clinical metformin glucose-lowering agent 1957, this medicine has emerged first-line pharmacological option support lifestyle interventions management type 2 diabetes (T2D). It acts through multiple cellular pathways, principally gut, liver and muscle, counter insulin resistance lower blood glucose without weight gain or risk overt hypoglycaemia. Other effects include improvements lipid metabolism, decreased inflammation long-term cardiovascular risk. is conveniently combined with other medications, be prescribed prediabetes reduce progression T2D, used some regions assist glycaemic control pregnancy. Consistent diversity actions, established safety profile cost-effectiveness, being assessed further possible applications. The requires adequate renal function drug elimination, may cause initial gastrointestinal side effects, which moderated by taking meals using an extended-release formulation. Thus, serves valuable therapeutic resource throughout natural history T2D.

Language: Английский

---

View on Metformin: Antidiabetic and Pleiotropic Effects, Pharmacokinetics, Side Effects, and Sex-Related Differences

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 478 - 478

Published: April 8, 2024

Metformin is a synthetic biguanide used as an antidiabetic drug in type 2 diabetes mellitus, achieved by studying the bioactive metabolites of Galega officinalis L. It also off-label for various other diseases, such subclinical diabetes, obesity, polycystic ovary syndrome, etc. In addition, metformin proposed add-on therapy several conditions, including autoimmune neurodegenerative and cancer. Although has been many decades, it still subject pharmacodynamic pharmacokinetic studies light its extensive use. acts at mitochondrial level inhibiting respiratory chain, thus increasing AMP/ATP ratio and, subsequently, activating AMP-activated protein kinase. However, mechanisms have proposed, binding to presenilin enhancer 2, GLP1 release, modification microRNA expression. Regarding pharmacokinetics, after oral administration, absorbed, distributed, eliminated, mainly through renal route, using transporters cationic solutes, since exists ionic molecule physiological pH. this review, particular consideration paid literature data from last 10 years, deepening study clinical trials inherent new uses metformin, differences effectiveness safety observed between sexes, unwanted side effects. For objective, was evaluated both VigiBase EudraVigilance, respectively, WHO European databases reported adverse reactions, assess extent effects real-life

Language: Английский

---

Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5694 - 5694

Published: May 23, 2024

According to the WHO 2016 classification, glioblastoma is most prevalent primary tumor in adult central nervous system (CNS) and categorized as grade IV. With an average lifespan of about 15 months from diagnosis, has a poor prognosis presents significant treatment challenge. Aberrant angiogenesis, which promotes neovascularization prospective target for molecular treatment, one its unique aggressive characteristics. Recently, existence glioma stem cells (GSCs) within tumor, are tolerant chemotherapy radiation, been linked highly form glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations clinical trials demonstrating encouraging results. This suggests need discover new options. Glioblastoma numerous cancers metformin, anti-hyperglycemic medication belonging Biguanides family, used first-line therapy type 2 diabetes mellitus (T2DM), it shown both vitro vivo anti-tumoral activity. Based on these findings, repurposed, inhibition many oncopromoter mechanisms and, result, identified pathways involved. Metformin inhibits cancer cell growth by blocking LKB1/AMPK/mTOR/S6K1 pathway, leading selective death GSCs inhibiting proliferation CD133+ cells. It minimal impact differentiated normal human The systematic retrieval information was performed PubMed. A total 106 articles were found search metformin Out six Meta-analyses, Randomized Controlled Trials, trials, Systematic Reviews. rest Literature review articles. These years 2011 2024. Appropriate studies isolated, important each them understood entered into database this article. use searched clinicaltrials.gov. In article, we examine evaluate metformin's possible effects glioblastoma, determining whether or may appropriately function anti-angiogenic substance be safely added management patients.

Language: Английский

---

Utilising Endogenous Biomarkers in Drug Development to Streamline the Assessment of Drug–Drug Interactions Mediated by Renal Transporters: A Pharmaceutical Industry Perspective

Clinical Pharmacokinetics, Journal Year: 2024, Volume and Issue: 63(6), P. 735 - 749

Published: June 1, 2024

The renal secretion of many drugs is facilitated by membrane transporters, including organic cation transporter 2, multidrug and toxin extrusion protein 1/2-K anion transporters 1 3. Inhibition these can reduce excretion thereby pose a safety risk. Assessing the risk inhibition investigational remains key focus in evaluation drug-drug interactions (DDIs). Current methods to predict DDI are based on generating vitro data followed clinical assessment using recommended exogenous probe substrate for individual drug transporter. More recently, monitoring plasma-based urine-based endogenous biomarkers transporter-mediated DDIs early phase I studies represents promising approach facilitate, improve potentially avoid conventional studies. This perspective reviews evidence use DDI, evaluates how may help expand toolkit offers some potential knowledge gaps. A conceptual framework that complement current paradigm predicting outlined.

Language: Английский

---

Recent advances in the management of knee osteoarthritis: a narrative review

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 21, 2025

Knee osteoarthritis (OA) is a common condition that causes pain and reduces the quality of life for many people. It also leads to high health financial costs. Managing knee OA requires using different methods together best results. This review overviews current therapeutic options pain, focusing on their efficacy, safety, potential roles in clinical practice. Topical treatments, such as NSAIDs capsaicin, offer significant relief with minimal systemic side effects are suitable initial therapy, nonpharmacologic interventions like exercise and, when relevant, weight loss. Oral analgesics, including acetaminophen opioids, have limited efficacy serious effects, making them appropriate only short-term or rescue therapy. Intra-articular injections, corticosteroids, hyaluronic acid, platelet rich plasma, demonstrate varying levels safety. Nutritional supplements, curcumin, Boswellia serrata , glucosaminechondroitin combinations, modest benefits used adjuncts standart treatment. Nonpharmacological transcutaneous electrical nerve stimulation (TENS), acupuncture, local heat provide variable should be customized based individual patient responses. Targeted biologic agents, antibodies TNF-α, IL-1, NGF, hold promise more precise relief; however, further research required establish routine use. Treating personalized, combining several methods. Research must continue improve treatments make safer.

Language: Английский

---

Linking Cardiovascular Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): The Role of Cardiometabolic Drugs in MASLD Treatment

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 324 - 324

Published: Feb. 23, 2025

The link between cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver (MASLD) is well-established at both the epidemiological pathophysiological levels. Among common mechanisms involved in development progression of diseases, oxidative stress inflammation, insulin resistance, lipid metabolism deterioration, hepatokines, gut dysbiosis along with genetic factors have been recognized to play a pivotal role. Pharmacologic interventions drugs targeting modifiable cardiometabolic risk factors, such as T2DM, dyslipidemia, hypertension, are reasonable strategy prevent CVD MASLD. Recently, novel drug for steatohepatitis (MASH), resmetirom, has shown positive effects regarding risk, opening new opportunities therapeutic approach MASLD CVD. This review provides current knowledge on epidemiologic association morbidity mortality enlightens possible underlying pathophysiologic linking role anti-hypertensive drugs, hypolipidemic agents, glucose-lowering medications, acetylsalicylic acid, thyroid hormone receptor-beta agonist also discussed. Metformin failed prove beneficial progression. Studies administration thiazolinediones suggest effectiveness improving steatosis, steatohepatitis, fibrosis, while newer categories agents GLP-1Ra SGLT-2i currently being tested their efficacy across whole spectrum Statins alone or combination ezetimibe yielded promising results. conduction long-duration, large, high-quality, randomized-controlled trials aiming assess by biopsy reverse great importance.

Language: Английский

---

Mitochondria and Oxidative Stress as a Link between Alzheimer’s Disease and Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14450 - 14450

Published: Sept. 22, 2023

This review is devoted to the problems of common features linking metabolic disorders and type 2 diabetes with development Alzheimer’s disease. The pathogenesis disease closely intersects mechanisms development, an important risk factor for both pathologies aging. Common pathological include factors in oxidative stress, neuroinflammation, insulin resistance, amyloidosis, as well impaired mitochondrial dysfunctions increasing cell death. currently available drugs treatment have limited therapeutic efficacy. It note that used treat disease, particular acetylcholinesterase inhibitors, show a positive potential diabetes, while can also prevent number characteristic A promising direction search strategy may be creation complex multi-target neuroprotective affect specific targets

Language: Английский

---

A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 21, 2024

Introduction Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers disability progression that insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing metformin for PMS. The objective this clinical trial is evaluate whether metformin, as add-on treatment, superior placebo delaying disease Methods analysis MACSiMiSE-BRAIN multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled trial, conducted at five sites Belgium. Enrollment 120 PMS planned. Each participant will undergo screening visit assessment baseline magnetic resonance imaging (MRI), tests, questionnaires, safety laboratory assessment. Following randomization, participants be assigned either the (metformin) or group. Subsequently, they 96-week follow-up period. primary outcome change walking speed, measured Timed 25-Foot Walk Test, from 96 weeks. Secondary measures include neurological (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) hand function (9-Hole Peg test). Annual brain MRI performed assess evolution volumetry diffusion metrics. As may not progress all domains, composite outcome, Overall Response Score additionally evaluated an exploratory outcome. Other outcomes consist paramagnetic rim lesions, 2-minute test health economic analyses well both patient- caregiver-reported like EQ-5D-5L, Multiple Sclerosis Impact Scale Caregiver Strain Index. Ethics dissemination Clinical authorization regulatory agencies [Ethical Committee Federal Agency Medicines Health Products (FAMHP)] was obtained after submission centralized European Trial Information System. results disseminated scientific conferences, peer-reviewed publications, patient associations general public. registration ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.

Language: Английский

---

Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 18, 2024

Abstract Mitochondria play a central role in cellular energy metabolism, and their dysfunction is increasingly recognized as critical factor the pathogenesis of diabetes-related cardiac pathophysiology, including vulnerability to ischemic events that culminate myocardial infarction on one hand ventricular arrhythmias other. In diabetes, hyperglycemia altered metabolic substrates lead excessive production reactive oxygen species (ROS) by mitochondria, initiating cascade oxidative stress damages mitochondrial DNA, proteins, lipids. This injury compromises efficiency phosphorylation, leading impaired ATP production. The resulting deficit damage contribute functional abnormalities cells, placing heart at an increased risk electromechanical irreversible cell death response insults. While mitochondria are often considered be relatively autonomous entities capacity produce ROS, highly dynamic nature within elaborate network closely-coupled organelles occupies 30–40% cardiomyocyte volume fundamental ability exert intricate regulation over global function. this article, we review evidence linking properties overall function its injury. We then highlight select studies ultrastructural alterations driven changes fission, fusion mitophagy promoting diabetic heart.

Language: Английский

---