Metformin clinical trials

Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Silvio E. This work received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

ES-R has nothing to disclose. He has participated on clinical trial steering, executive or publications committees for Boehringer Ingelheim, AstraZeneca, and Daiichi Sankyo. He has served as a member of data monitoring committees for Novo Nordisk and Intarcia. Both authors were responsible for drafting the article and revising it critically for important intellectual content. Both authors approved the version to be published. Reprints and Permissions. Sanchez-Rangel, E. Metformin: clinical use in type 2 diabetes.

Diabetologia 60, — Download citation. Received : 11 April Accepted : 17 May Published : 02 August Issue Date : September Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Download PDF. Abstract Metformin is one of the most popular oral glucose-lowering medications, widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus.

Use as first-line therapy As noted, metformin is preferred by most guideline committees as the initial therapy in individuals not able to achieve glycaemic targets despite diet and other lifestyle interventions [ 5 ].

Full size image. Use in combination therapy Metformin is also efficacious when used in various combination regimens. Metformin and sulfonylureas The combination of metformin and a sulfonylurea is amongst the most commonly prescribed. Non-glycaemic effects Once the cardiovascular benefits of metformin were suggested following clinical trials [ 26 ], interest into the pleiotropic effects of the drug arose.

Lactic acidosis A much rarer but more concerning adverse consequence of biguanide therapy is lactic acidosis. B12 deficiency Vitamin B12 malabsorption is another potential side effect of metformin, now convincingly demonstrated through multiple case reports and cross-sectional and longitudinal studies. Dosing considerations In order to minimise GI side effects, metformin should be taken with meals and initiated at a low dose, typically mg once or twice daily with gradual increases i.

Guidelines Metformin is recommended as a first-line drug for the management of type 2 diabetes in most treatment guidelines [ 11 ], a position based on its efficacy, low cost, relative safety and the cardiovascular benefits shown by the UKPDS.

Future directions Several recent, large cardiovascular outcome safety trials have found significant cardiovascular and, in some circumstances, renal benefits from non-biguanide therapies e.

Conclusions With widespread use for more than two decades, metformin remains ensconced as an essential drug in the growing pharmacopeia for type 2 diabetes. References 1. Maroc Med — Google Scholar 3. Lancet — Article Google Scholar View author publications.

Ethics declarations Funding This work received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Duality of interest ES-R has nothing to disclose. Contribution statement Both authors were responsible for drafting the article and revising it critically for important intellectual content.

Electronic supplementary material. Rights and permissions Reprints and Permissions. About this article. The dynamics of autophagy are controlled by autophagy-related genes and by one of the central regulators of metabolism, AMPK the target of metformin.

Autophagy also affects stem cells and cellular senescence. When the process of autophagy fails, the result is a state of chronic inflammation and degeneration in many organ systems. Numerous studies have documented the metabolic benefits conferred by the glucose lowering agent metformin.

In animal models, metformin has been shown to increase both lifespan and health-span, and a clinical trial NCT is currently ongoing to determine whether this effect translates to humans, with additional investigation into how the medication alters the adult human transcriptome.

In vitro studies demonstrate metformin's ability to mitigate aging- and disease-related inflammation, oxidative damage, and diminished autophagy. Additionally, there are numerous cohort, case-control and meta-analysis studies confirming metformin's reduction in cancer-related death via hypothesized activity in the relevant mTOR, human epidermal growth factor receptor 2 HER2 , micro-Ribosomal Nucleic Acid miRNA and transcription growth factor alpha TGF-alpha pathways and processes.

This study will provide preliminary data for such a proposal, and it will fill a knowledge gap regarding the use of validated biomarkers in this arena. It will also contribute significantly to the anti-aging literature. The primary objective of this proposal is to validate the autophagy-related experimental design by using leucocyte LC3 as a marker of autophagy and cellular senescence in humans.

Aim: Demonstrate that metformin therapy will increase cellular autophagy as an inverse correlate of aging as measured by increases in LC3 scores. Layout table for study information Study Type : Interventional Clinical Trial Estimated Enrollment : 25 participants Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: This is a double-blind, approximate placebo-controlled trial of 12 weeks of metformin vs.

CaCO3 Placebo among adult patients with prediabetes. Drug: Metformin Total daily dose titrated up to mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks. Drug: Placebo Oral Tablet Total daily dose titrated up to mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks. LC3-II is a widely used marker to monitor autophagosome formation by quantitation of the number of LC3-labeled puncta autophagosomes, or "dots" per cell detected by fluorescence microscopy.

An increase in LC3 puncta formation denotes an increase in autophagic activity. Talk with your doctor and family members or friends about deciding to join a study. Ushering a New Era of Interventions. The Targeting Aging with Metformin TAME Trial is a series of nationwide, six-year clinical trials at 14 leading research institutions across the country that will engage over 3, individuals between the ages of Why Metformin?

Metformin is an FDA-approved drug used successfully to treat diabetes for more than 60 years. Trial sites secured. Years of trials, once launched.

Participants, ages , to be engaged. Donate here. Concurrent Biomarkers Study The TAME Trial will also enhance our understanding of the biomarkers of aging through a concurrent study: TAME BIO will provide a foundation for future biomarker discovery and validation, play an important role in evaluating the effects metformin on TAME trial participants, and accelerate the pace of geroscience research. Seven patients Patients agreed or strongly agreed that they would participate in a telemedicine-enabled clinical trial in the future.

Conclusion: To our knowledge, this interventional oncology clinical trial is the first to be conducted through telemedicine.