IJCRT Peer-Reviewed (Refereed) Journal as Per New UGC Rules.
ISSN Approved Journal No: 2320-2882 | Impact factor: 7.97 | ESTD Year: 2013
Scholarly open access journals, Peer-reviewed, and Refereed Journals, Impact factor 7.97 (Calculate by google scholar and Semantic Scholar | AI-Powered Research Tool) , Multidisciplinary, Monthly, Indexing in all major database & Metadata, Citation Generator, Digital Object Identifier(CrossRef DOI)
| IJCRT Journal front page | IJCRT Journal Back Page |
Paper Title: Tracing Thematic Parallels; A Comparative Analysis of Mother Mary Comes to Me and Kambilikandathe Kalbharanikal
Author Name(s): Ancy Cyriac
Published Paper ID: - IJCRT2511829
Register Paper ID - 297504
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511829 and DOI :
Author Country : Indian Author, India, 686001 , Kottayam, 686001 , | Research Area: Medical Science All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511829 Published Paper PDF: download.php?file=IJCRT2511829 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511829.pdf
Title: TRACING THEMATIC PARALLELS; A COMPARATIVE ANALYSIS OF MOTHER MARY COMES TO ME AND KAMBILIKANDATHE KALBHARANIKAL
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Medical Science All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h49-h53
Year: November 2025
Downloads: 177
E-ISSN Number: 2320-2882
Abstract: This paper aims at finding thematic parallels between two memoirs- Arundhati Roy's Mother Mary Comes to Me and Babu Abraham's Kambilikandathe Kalbharanikal. Even though these texts differ largely in scope and style, their themes converge at many points. Through a comparative analysis, this paper brings to light the common thematic threads across the texts.
Licence: creative commons attribution 4.0
mother, Biblical allusions
Paper Title: Rediscovering Traditional Knowledge Systems for Contemporary Global Sustainability
Author Name(s): Brojendra Nath Dey, Asish Mitra
Published Paper ID: - IJCRT2511828
Register Paper ID - 296774
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511828 and DOI :
Author Country : Indian Author, India, 721171 , KTPP Township, 721171 , | Research Area: Arts1 All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511828 Published Paper PDF: download.php?file=IJCRT2511828 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511828.pdf
Title: REDISCOVERING TRADITIONAL KNOWLEDGE SYSTEMS FOR CONTEMPORARY GLOBAL SUSTAINABILITY
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Arts1 All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h36-h48
Year: November 2025
Downloads: 169
E-ISSN Number: 2320-2882
Traditional knowledge systems, developed over millennia by indigenous communities worldwide, represent valuable repositories of practical wisdom for addressing contemporary global challenges. This review examines the scientific validation, integration, and application of ancient knowledge in modern contexts across medicine, agriculture, environmental management, and technology. The analysis synthesizes findings from peer-reviewed studies demonstrating that traditional practices in Ayurveda, Traditional Chinese Medicine, and indigenous ecological management offer evidence-based solutions to pressing issues including climate change, biodiversity loss, sustainable development, and healthcare accessibility. This review explores the antimicrobial efficacy of medicinal plants such as turmeric and neem, the neuroscientific validation of meditation and yoga practices, the nanotechnology precedents in ancient metallurgy, and the sustainability of traditional water management and agricultural systems. Through comparative analysis, we demonstrate that ancient approaches often exhibit superior environmental sustainability, cost-effectiveness, and long-term viability compared to conventional modern methods, though with varying immediate efficacy rates across different domains. However, significant challenges persist, including bio-piracy threats, inadequate intellectual property protection, and the erosion of traditional knowledge due to globalization and climate change. This review proposes an integrated framework combining rigorous scientific validation with ethical safeguards for knowledge holders' rights, emphasizing interdisciplinary research, community-based documentation, and equitable benefit-sharing mechanisms. The strategic integration of validated traditional knowledge into mainstream science, policy, and practice represents a critical pathway toward achieving Sustainable Development Goals while preserving cultural heritage and promoting inclusive, resilient development models for the 21st century (1, 2, 3).
Licence: creative commons attribution 4.0
Ancient Technology, Climate Adaptation, Indigenous Ecological Knowledge, Scientific Validation, , Sustainable Development, Traditional Knowledge
Paper Title: ESG Integration and Sustainable Investment: The Role of Green Bonds in Portfolio Diversification
Author Name(s): Prof. Nidhi Vaidhya
Published Paper ID: - IJCRT2511827
Register Paper ID - 297347
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511827 and DOI :
Author Country : Indian Author, India, 452005 , Indore, 452005 , | Research Area: Management All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511827 Published Paper PDF: download.php?file=IJCRT2511827 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511827.pdf
Title: ESG INTEGRATION AND SUSTAINABLE INVESTMENT: THE ROLE OF GREEN BONDS IN PORTFOLIO DIVERSIFICATION
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Management All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h28-h35
Year: November 2025
Downloads: 140
E-ISSN Number: 2320-2882
Environmental, Social, and Governance (ESG) integration is increasingly becoming a cornerstone of modern investment strategies, driven by the growing demand for sustainability and ethical responsibility in the financial sector. Among various ESG-aligned instruments, green bonds have emerged as a key vehicle for channeling capital toward environmentally beneficial projects. This research paper explores the critical intersection of ESG integration and sustainable investment, with a specific focus on the role of green bonds in enhancing portfolio diversification. The paper begins by reviewing the evolution and structure of green bonds, emphasizing their alignment with the ESG framework and their capacity to support climate-resilient infrastructure and renewable energy projects. It further examines how investors--ranging from institutional to retail--are incorporating ESG metrics into their decision-making processes to not only meet regulatory expectations but also to capture long-term financial value and mitigate risk. Through a comparative analysis of conventional and green bond performance across global markets, this study investigates whether green bonds offer competitive returns while contributing to portfolio diversification. The findings suggest that green bonds, while slightly constrained in terms of liquidity and issuance volume compared to traditional fixed-income instruments, exhibit lower volatility and align with risk-adjusted return profiles that are increasingly favored by sustainability-focused investors. Moreover, the research highlights the portfolio optimization potential of green bonds when included alongside equities and other asset classes. By employing mean-variance analysis and ESG screening models, the paper demonstrates that green bonds enhance the environmental footprint of a portfolio without significantly compromising financial performance. Case studies and empirical data from markets such as the EU, the US, and emerging economies provide further evidence of green bonds' growing impact. The study concludes that the integration of ESG principles through instruments like green bonds not only advances the goals of sustainable development but also strengthens investment portfolios against market and environmental uncertainties. It recommends broader adoption of green bonds, supportive regulatory frameworks, and increased transparency in ESG reporting to foster sustainable financial ecosystems. This research contributes to the expanding literature on sustainable finance by offering a comprehensive view of how green bonds can act as a strategic asset in ESG-aligned portfolio management. It provides valuable insights for investors, policymakers, and financial institutions aiming to balance financial objectives with sustainability imperatives in the evolving global economy.
Licence: creative commons attribution 4.0
Green Bonds, ESG Integration, Sustainable Investment, Portfolio Diversification, Sustainable Finance
Paper Title: Villa online booking website
Author Name(s): Paresh Maindarge, Sanket Argade, Abhishek joshi, Aditya pawar
Published Paper ID: - IJCRT2511826
Register Paper ID - 297022
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511826 and DOI :
Author Country : Indian Author, India, 413504 , Bhoom, 413504 , | Research Area: Science and Technology Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511826 Published Paper PDF: download.php?file=IJCRT2511826 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511826.pdf
Title: VILLA ONLINE BOOKING WEBSITE
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Science and Technology
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h21-h27
Year: November 2025
Downloads: 132
E-ISSN Number: 2320-2882
Abstract:-The Villa Booking Website is an online platform designed to simplify the process of discovering, comparing, and reserving villas for vacations, events, and long-term stays. The website provides users with an intuitive interface to browse villas based on location, budget, amenities, and availability. It aims to bridge the gap between villa owners and potential guests by offering a seamless booking experience supported by secure payment options and real-time reservation management. The system enhances user convenience through features such as advanced search filters, image galleries, reviews, and automated booking confirmations. By digitizing the traditional villa rental process, the platform increases accessibility, reduces manual effort, and provides a reliable solution for both travelers and property owners.
Licence: creative commons attribution 4.0
Villa BookingOnline Reservation SystemHospitality ManagementTourism TechnologyWeb ApplicationProperty Management SystemOnline Accommodation BookingVacation RentalsTravel and TourismUser AuthenticationSecure Payment SystemReal-time AvailabilityBooking ManagementDigital PlatformCustomer Experience
Paper Title: Maintenance Under Muslim Law
Author Name(s): M.KrishnaDevi, S.Abisha
Published Paper ID: - IJCRT2511825
Register Paper ID - 297215
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511825 and DOI :
Author Country : Indian Author, India, 621112 , Trichy, 621112 , | Research Area: Others area Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511825 Published Paper PDF: download.php?file=IJCRT2511825 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511825.pdf
Title: MAINTENANCE UNDER MUSLIM LAW
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Others area
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h15-h20
Year: November 2025
Downloads: 201
E-ISSN Number: 2320-2882
The topic is about Muslim Maintenance and the persons who are eligible to get maintenance under the Muslim law for wife, children, and daughter-in-law, grand-parents and grand-children. There are some sections that speaks about the purpose and critical analysis under the Muslim Law and the CRPC (code of criminal procedure) sections converted into BNSS (Bharatiya Nagarik Suraksha Sanhita ).
Licence: creative commons attribution 4.0
Paper Title: Deafy : AI-Powered Sign Language Communication Bridge
Author Name(s): Anuradha Popat Patil, Piyusha Santosh Awate, Sakshi Ajit Koganole, Sanjana Sambhaji Magdum, Pravin Karve
Published Paper ID: - IJCRT2511824
Register Paper ID - 297474
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511824 and DOI :
Author Country : Indian Author, India, 416103 , Shirol, 416103 , | Research Area: Science and Technology Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511824 Published Paper PDF: download.php?file=IJCRT2511824 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511824.pdf
Title: DEAFY : AI-POWERED SIGN LANGUAGE COMMUNICATION BRIDGE
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Science and Technology
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h5-h14
Year: November 2025
Downloads: 139
E-ISSN Number: 2320-2882
The communication gap between hearing and speech-impaired individuals and the general population remains a major challenge in inclusive human interaction. To address this issue, we present Echo Sign, a bidirectional communication system that translates sign language into audio and audio into sign language in real time. The system is implemented using a Python-based backend integrating machine learning models for gesture recognition and speech synthesis for audio generation. The architecture employs computer vision for hand gesture detection, speech-to-text processing for audio input, and 3D animated sign rendering for sign output. Echo Sign successfully bridges the accessibility divide by enabling smooth, natural communication between differently-abled and non-disabled users. The paper discusses the system architecture, functionality, and integration of multiple AI components within a unified framework. Future enhancements aim to improve model precision, expand gesture datasets, and deploy Echo Sign as a cross-platform application for real-world accessibility and scalability.
Licence: creative commons attribution 4.0
Sign Language Recognition, Speech Synthesis, Bidirectional Communication, Machine Learning, Computer Vision, Accessibility, Human-Computer Interaction
Paper Title: Psychological Dimensions of Athletic Performance: A Focus on Mood and Mental Training in Basketball
Author Name(s): Prof. Shekhar Singh, Prasoon Kumar Singh
Published Paper ID: - IJCRT2511823
Register Paper ID - 297274
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511823 and DOI :
Author Country : Indian Author, India, 222002 , Jaunpur, 222002 , | Research Area: Arts1 All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511823 Published Paper PDF: download.php?file=IJCRT2511823 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511823.pdf
Title: PSYCHOLOGICAL DIMENSIONS OF ATHLETIC PERFORMANCE: A FOCUS ON MOOD AND MENTAL TRAINING IN BASKETBALL
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Arts1 All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: h1-h4
Year: November 2025
Downloads: 137
E-ISSN Number: 2320-2882
The integration of psychology into sports science has revolutionized athletic training, emphasizing the mental dimensions of performance alongside physical conditioning. This article explores the pivotal role of psychological factors particularly mood and mental training in shaping athletic outcomes, with a focused lens on basketball. As a sport demanding both physical agility and psychological resilience, basketball exemplifies the need for mental preparedness in high-pressure scenarios. Psychological skills such as focus, emotional regulation, and confidence are shown to influence decision-making, team cohesion, and individual performance. Mood, a critical psychological variable, significantly affects an athlete's ability to perform, with positive emotional states linked to enhanced vigor and strategic clarity, while negative moods may impair concentration and execution. The Brunel Mood Scale (BRUMS) emerges as a valuable tool for assessing mood profiles, enabling coaches and psychologists to tailor interventions that support optimal mental states. Techniques such as visualization, mindfulness, and cognitive restructuring are highlighted as effective strategies for mood regulation and performance enhancement. By recognizing and addressing the psychological needs of athletes, particularly in basketball, this study underscores the importance of mental training programs in fostering resilience, well-being, and competitive excellence. The findings advocate for a holistic approach to athletic development, where mental strength is cultivated as rigorously as physical skill.
Licence: creative commons attribution 4.0
Sports Psychology, Athletic Performance, Mood Regulation, Mental Training, Basketball, Brunel Mood Scale (BRUMS) and Emotional Resilience
Paper Title: Assessment of Awareness and Interdisciplinary Collaboration among Medical Professionals on Periodontal Systemic Health
Author Name(s): Dr Adithya S N, Dr Aishwarya S, Dr archana.b, Dr.nimisha mithradas, Dr.Navina ravindran
Published Paper ID: - IJCRT2511822
Register Paper ID - 297372
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511822 and DOI :
Author Country : Indian Author, India, 600026 , Chennai , 600026 , | Research Area: Humanities All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511822 Published Paper PDF: download.php?file=IJCRT2511822 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511822.pdf
Title: ASSESSMENT OF AWARENESS AND INTERDISCIPLINARY COLLABORATION AMONG MEDICAL PROFESSIONALS ON PERIODONTAL SYSTEMIC HEALTH
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Humanities All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: g978-g996
Year: November 2025
Downloads: 118
E-ISSN Number: 2320-2882
Background: Periodontal disease is a chronic inflammatory condition that affects the supporting tissues of the teeth and is increasingly recognized as having systemic implications. Over the past two decades, evidence has accumulated linking periodontitis with systemic conditions such as diabetes mellitus, cardiovascular disease, adverse pregnancy outcomes, respiratory disease, and immune dysregulation [1-7]. Despite this, integration between dental and medical care remains limited in many settings, including India, resulting in missed prevention and referral opportunities [8,13,17]. Objective: To synthesize the current literature on periodontal-systemic links, to report and interpret the findings of a 24-question survey of Indian medical professionals assessing awareness, attitudes, and practices, and to propose actionable steps to strengthen medical-dental collaboration. Methods: We conducted a descriptive review of 20 peer-reviewed articles addressing periodontal-systemic associations, mechanisms, clinical outcomes, and interprofessional integration strategies [1-20]. We compared and contextualized these findings with results from a structured 24-item questionnaire administered to medical professionals in India. The questionnaire covered knowledge, attitudes, referral behavior, and perceived barriers to collaboration. Survey responses were summarized as proportions and integrated into the discussion to identify gaps and opportunities. Results: The survey showed high general awareness that oral health affects systemic health (?82%), and strong recognition of the specific links between periodontitis and diabetes (?84%) and cardiovascular disease (?76%). However, referral and collaborative behaviors lagged--fewer than half reported routine referral to dental services or regular interprofessional meetings. Knowledge gaps persisted for some mechanistic concepts (e.g., bacteremia and immune modulation) and practical measures (e.g., which medications cause gingival overgrowth), consistent with the literature indicating partial but inconsistent translation of evidence into practice [2-7,11,12]. Conclusion: Although awareness among Indian medical professionals is promising, meaningful integration into clinical practice is incomplete. To close this translation gap, curricular reform, structured interprofessional education, referral pathways, and institutional policies supporting integrated care are recommended. These measures align with best-practice suggestions found in the literature [15,16,18-20].
Licence: creative commons attribution 4.0
Periodontal-Systemic Health, Awareness, Attitudes, and Practices,Diabetes Mellitus,Bacteremia.
Paper Title: Demographic Influences on Mobile Shopping Apps Adoption: An Empirical Study Using the UTAUT Framework
Author Name(s): Meenu, Dr. Manpreet Kaur
Published Paper ID: - IJCRT2511821
Register Paper ID - 297275
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511821 and DOI : https://doi.org/10.56975/ijcrt.v13i11.297275
Author Country : Indian Author, India, 147301 , Mandi Gobindgarh, , 147301 , | Research Area: Commerce All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511821 Published Paper PDF: download.php?file=IJCRT2511821 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511821.pdf
Title: DEMOGRAPHIC INFLUENCES ON MOBILE SHOPPING APPS ADOPTION: AN EMPIRICAL STUDY USING THE UTAUT FRAMEWORK
DOI (Digital Object Identifier) : https://doi.org/10.56975/ijcrt.v13i11.297275
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Commerce All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: g970-g977
Year: November 2025
Downloads: 154
E-ISSN Number: 2320-2882
This research examines the factors influencing the adoption of mobile shopping apps among Indian consumers using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework. With India's rapid growth in e-commerce, rising internet access, and increasing smartphone use, consumer behaviour has shifted toward mobile shopping. The study surveyed 300 users of mobile shopping apps in Haryana through structured questionnaires. It employed quantitative methods, including t-tests and ANOVA, to analyse the impact of demographic factors such as age, gender, and residential status. Results reveal significant differences in adoption intentions across demographic groups. Specifically, younger users demonstrate higher engagement due to convenience and affordability; males show greater influence from subjective norms and facilitating conditions; and rural consumers are more affected by social factors than urban consumers. The study highlights the importance of tailored strategies, improved app usability, and digital literacy initiatives to promote the adoption of mobile shopping. These findings offer practical insights for businesses, marketers, developers, and policymakers seeking to enhance user experience and expand market reach in India's mobile e-commerce sector.
Licence: creative commons attribution 4.0
Mobile shopping, M-shopping apps, UTAUT, Adoption
Paper Title: Pharmacological Management of Type 2 Diabetes: A Comprehensive Review of Metformin's Mechanisms and Enduring First-Line Efficacy
Author Name(s): Vedant Shailendra Borkar, Rakshit Rakesh Kanojiya, Mayur Dharmraj Santape, Mohit Rajesh Nandanwar, Rahela Anjum
Published Paper ID: - IJCRT2511820
Register Paper ID - 297501
Publisher Journal Name: IJPUBLICATION, IJCRT
DOI Member ID: 10.6084/m9.doi.one.IJCRT2511820 and DOI :
Author Country : Indian Author, India, 440014 , Nagpur, 440014 , | Research Area: Pharmacy All Published Paper URL: http://ijcrt.org/viewfull.php?&p_id=IJCRT2511820 Published Paper PDF: download.php?file=IJCRT2511820 Published Paper PDF: http://www.ijcrt.org/papers/IJCRT2511820.pdf
Title: PHARMACOLOGICAL MANAGEMENT OF TYPE 2 DIABETES: A COMPREHENSIVE REVIEW OF METFORMIN'S MECHANISMS AND ENDURING FIRST-LINE EFFICACY
DOI (Digital Object Identifier) :
Pubished in Volume: 13 | Issue: 11 | Year: November 2025
Publisher Name : IJCRT | www.ijcrt.org | ISSN : 2320-2882
Subject Area: Pharmacy All
Author type: Indian Author
Pubished in Volume: 13
Issue: 11
Pages: g954-g969
Year: November 2025
Downloads: 129
E-ISSN Number: 2320-2882
For more than 60 years, Metformin, a synthetic biguanide chemically derived from Galega officinalis, has been the first and most frequently chosen one of the first-line antihyperglycemic agents in the treatment of Type 2 Diabetes Mellitus (T2DM) patients. Its multifactorial mechanism of action in conjunction with a good safety profile and some cardio-protective effects make long-term use essentially the main reason for its continuous effectiveness. The major part of antidiabetic effect is due to the inhibition of Hepatic Glucose Production (HGP). Metformin after it is delivered to the liver cell via Organic Cation Transporter 1 (OCT1), only mildly inhibits mitochondrial respiratory chain Complex I. Due to the inhibition of oxidative phosphorylation, the cell experiences energetic stress; hence the AMP/ATP ratio increases and the irradiated AMP-Activated Protein Kinase (AMPK) is one. The activated AMPK then down-regulates the genes for gluconeogenesis (for example, PEPCK, G6Pase), glucose production being lowered accordingly. Metformin also alters the liver in a way that does not depend on AMPK. One of those ways involves glucagon ceasing stimulation of the cAMP pathway and at the same time inhibiting mitochondrial glycerol-3-phosphate dehydrogenase (mGPD). On the top of that, metformin doesn't depend entirely on the liver (extrahepatic/gut-mediated) mechanisms. Most of metformin's effect occurs in the intestine hence muscle glucose uptake is a result of increased gut glucose uptake by metformin. In addition, incretin hormone (GLP-1 and PYY) secretion which, among other things, is the main cause of the weight-neutral/weight-loss effect in metformin treated individuals, is also increased. Metformin is usually indicated to be the cause of an HbA1c reduction effect of 1.0% to 1.5%. The landmark UK Prospective Diabetes Study (UKPDS) provided the main proof of metformin's supremacy by demonstrating a substantial decrease of the first-time myocardial infarction and all-cause mortality in overweight individuals - a cardiovascular protection effect, which was prolonged and deepened for 20 years ("legacy effect"). In general, the medication is safe but some dose-related gastrointestinal symptoms have been reported as the most common side effects. The most important med, though seldom, risk is Metformin-Associated Lactic Acidosis (MALA) which mainly occurs in patients with renal impairment (eGFR <30 mL/min/1.73 m2). Also, the long-term exposure requires the monitoring of Vitamin B12 deficiency. In addition to that, Metformin has a few more potential effects on the positive side like anticancer capability via IMPK-mTOR pathway suppression, a good effect on PCOS and probably a gero protective agent (the focus of the TAME Trial). New drug classes (SGLT2i, GLP-1RA) with solid CVOT data are slowly but surely putting metformin in second place for patients with established cardiovascular disease as first-line treatment, however, it remains the most logical, evidence-based, cost-effective, and indispensable foundation for pharmacological intervention of T2DM worldwide.
Licence: creative commons attribution 4.0
Type 2 Diabetes Mellitus (T2DM), Metformin, Antihyperglycemic Agents, Mechanism of Action (or Metformin's Mechanisms), Hepatic Glucose Production (HGP), AMP-Activated Protein Kinase (AMPK), Biguanide

