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Clinical Pharmacokinetics Of Metformin Graham

Scicrunch | Searching In Literature

Scicrunch | Searching In Literature

The Journal of clinical investigation | May 3, 2007 Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug. Continue reading >>

Janna Duong - Google

Janna Duong - Google

GG Graham, J Punt, M Arora, RO Day, MP Doogue, J Duong, TJ Furlong, ... Clinical pharmacokinetics 50 (2), 81-98, 2011 JK Duong, SS Kumar, CM Kirkpatrick, LC Greenup, M Arora, TC Lee, ... Clinical pharmacokinetics 52 (5), 373-384, 2013 JK Duong, DM Roberts, TJ Furlong, SS Kumar, JR Greenfield, ... Diabetes, Obesity and Metabolism 14 (10), 963-965, 2012 JK Duong, TJ Furlong, DM Roberts, GG Graham, JR Greenfield, ... JK Duong, M Kroonen, SS Kumar, HL Heerspink, CM Kirkpatrick, ... European journal of clinical pharmacology 73 (8), 981-990, 2017 JK Duong, SS Kumar, TJ Furlong, CM Kirkpatrick, GG Graham, ... British journal of clinical pharmacology 79 (4), 617-623, 2015 D Roberts, J Duong, J Ray, K Williams, T Furlong JK Duong, MJ Griffin, D Hargrave, J Vormoor, D Edwards, AV Boddy British journal of clinical pharmacology 83 (8), 1713-1722, 2017 JK Duong, W Winter, S Choy, N Plock, H Naik, W Krauwinkel, SAG Visser, ... British journal of clinical pharmacology 83 (3), 487-497, 2017

The Role Of Genetic Factors And Kidney And Liver Function In Glycemic Control In Type 2 Diabetes Patients On Long-term Metformin And Sulphonylurea Cotreatment

The Role Of Genetic Factors And Kidney And Liver Function In Glycemic Control In Type 2 Diabetes Patients On Long-term Metformin And Sulphonylurea Cotreatment

The Role of Genetic Factors and Kidney and Liver Function in Glycemic Control in Type 2 Diabetes Patients on Long-Term Metformin and Sulphonylurea Cotreatment 1General Hospital Trbovlje, Rudarska cesta 9, 1420 Trbovlje, Slovenia 2Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia 3Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Zaloka cesta 2, 1000 Ljubljana, Slovenia Received 28 February 2014; Revised 18 May 2014; Accepted 21 May 2014; Published 9 June 2014 Copyright 2014 Jasna Klen et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study investigated the influence of genetic polymorphisms of metformin transporters on long-term glycemic control and lipid status in type 2 diabetes patients in the everyday clinical setting. In total 135 patients treated with combination of metformin and sulphonylurea for at least 6 months were genotyped for SLC22A1 rs628031 and SLC47A1 rs2289669 polymorphisms. Relatively good blood glucose control with median HbA1c 6.9 (6.47.6) % was achieved on prescribed metformin dosage of 2550 (20002550) mg per day. Only 28 (20.7%) patients experienced mild hypoglycemia events, while no severe hypoglycemia events were observed. Most patients had normal or mildly impaired renal function. Parameters indicating renal function were not correlated with fasting glucose, HbA1c, or lipid parameters. Rs628031 and rs2289669 had minor allele frequencies of 0.385 and 0.355, respectively, and were not associated with HbA1c levels. Rs628031 was margin Continue reading >>

Part B 367 Pathophysiology Of Dm1 And Dm2 - Medicine Bibliographies - In Harvard Style

Part B 367 Pathophysiology Of Dm1 And Dm2 - Medicine Bibliographies - In Harvard Style

Not logged in. Log in or create an account These are the sources and citations used to research Part B 367 Pathophysiology of DM1 and DM2. This bibliography was generated on Cite This For Me on Your Bibliography: Diabetesaustralia.com.au. (2016). Diabetes Australia. [online] Available at: [Accessed 29 Jul. 2016]. Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes Your Bibliography: Weir, G. and Bonner-Weir, S. (2004). Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes. Diabetes, 53(Supplement 3), pp.S16-S21. Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes Your Bibliography: Weir, G. and Bonner-Weir, S. (2004). Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes. Diabetes, 53(Supplement 3), pp.S16-S21. 2012 - Pearson Australia - Frenchs Forest, N.S.W. Your Bibliography: Bullock, S. and Hales, M. (2012). Principles of pathophysiology. Frenchs Forest, N.S.W.: Pearson Australia. Your Bibliography: Reutens, A. and Atkins, R. (2011). Epidemiology of Diabetic Nephropathy. Contributions to Nephrology, 170, pp.1-7. Mckenna's drug handbook for nursing and midwifery 2014 - Lippincott Williams & Wilkins Pty, Limited - Australia Your Bibliography: McKenna, L. and Mirkov, S. (2014). Mckenna's drug handbook for nursing and midwifery. 7th ed. Australia: Lippincott Williams & Wilkins Pty, Limited, pp.696-700. Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., Furlong, T. J., Greenfield, J. R., Greenup, L. C., Kirkpatrick, C. M., Ray, J. E., Timmins, P. and Williams, K. M. Your Bibliography: Graham, G., Punt, J., Arora, M., Day, R., Doogue, M., Duong, J., Furlong, T., Greenfield, J., Greenup, L., Kirkpatrick, C., Ray, J., Timmins, P. and Williams, K. (2011) Continue reading >>

Pharmacokinetics Of Metformin Pdf

Pharmacokinetics Of Metformin Pdf

Clinical Pharmacokinetics of Metformin (PDF Download Available) Official Full-Text Paper (PDF): Clinical Pharmacokinetics of Metformin. metformin hydrochloride tablets - FDA pharmacokinetics of metformin between patients with type 2 diabetes and normal Limited data from controlled pharmacokinetic studies of metformin in healthy Mechanism of Action Pharmacokinetics - FDA GLUMETZA (metformin hydrochloride) extended release tablet is an oral . pharmacokinetics of metformin because of the imbalance in the respective sizes of Clinical pharmacokinetics of metformin. - NCBI Clin Pharmacokinet. 2011 Feb;50(2):81-98. doi: 10.2165/11534750-000000000-00000. Clinical pharmacokinetics of metformin. Graham GG(1), Punt J, Arora can you buy tylenol if your under 18 M, Metformin pathways: pharmacokinetics and pharmacodynamics This summary briefly reviews the pharmacokinetics of metformin (Fig. 1) and highlights genes mediating the diverse pharmacological responses to metformin Pharmacokinetics and Pharmacodynamics of Metformin in Healthy or not metformin exhibits dose-dependent pharmacokinetics. 2,550 mg, and placebo) and a multiple-dose treatment of 850 mg metformin HC1 (3 times daily Clinical Pharmacokinetics of Metformin - Springer Link Clinical Pharmacokinetics of Metformin. Garry G. Graham,1 Jeroen Punt,1 Manit Arora,1 Richard O. Day,1 Matthew P. Doogue,2 Janna K. Duong,1. Timothy J. Pharmacokinetic-Pharmacodynamic Modeling of Metformin for the 10 Oct 2010 2011 Bentham Open. Open Access. Pharmacokinetic-Pharmacodynamic Modeling of Metformin for the. Treatment of Type II Diabetes Mellitus. Pharmacokinetic studies of metformin and - Semantic Scholar By applying this method, important pharmacokinetic parameters Cmax, Tmax, AUC0- Keywords: Metformin, glibenclamide, pharmacokinetic, pl Continue reading >>

Clinical Pharmacokinetics Of Metformin.

Clinical Pharmacokinetics Of Metformin.

1. Clin Pharmacokinet. 2011 Feb;50(2):81-98. doi: 10.2165/11534750-000000000-00000. Graham GG(1), Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ,Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. (1)Department of Pharmacology & Toxicology, St Vincents Clinical School, University of New South Wales, Sydney, New South Wales, Australia. [email protected] Metformin is widely used for the treatment of type 2 diabetes mellitus. It is abiguanide developed from galegine, a guanidine derivative found in Galegaofficinalis (French lilac). Chemically, it is a hydrophilic base which exists at physiological pH as the cationic species (>99.9%). Consequently, its passivediffusion through cell membranes should be very limited. The mean SD fractionaloral bioavailability (F) of metformin is 55 16%. It is absorbed predominatelyfrom the small intestine. Metformin is excreted unchanged in urine. Theelimination half-life (t(½)) of metformin during multiple dosages inpatients with good renal function is approximately 5 hours. From published dataon the pharmacokinetics of metformin, the population mean of its clearances were calculated. The population mean renal clearance (CL(R)) and apparent totalclearance after oral administration (CL/F) of metformin were estimated to be 510 130 mL/min and 1140 330 mL/min, respectively, in healthy subjects anddiabetic patients with good renal function. Over a range of renal function, thepopulation mean values of CL(R) and CL/F of metformin are 4.3 1.5 and 10.7 3.5 times as great, respectively, as the clearance of creatinine (CL(CR)). As theCL(R) and CL/F decrease approximately in proportion to CL(CR), the dosage ofmetformin should be reduced in patients with renal impairment in proportion tothe reduced CL(CR). The Continue reading >>

The Effect Of Dolutegravir On The Pharmacokinetics Of Metformin In Healthy Subjects

The Effect Of Dolutegravir On The Pharmacokinetics Of Metformin In Healthy Subjects

Dolutegravir (Tivicay; ViiV Healthcare, Research Triangle Park, NC) belongs to a novel class of antiretroviral drugs known as integrase strand transfer inhibitors (INSTIs) and blocks the activity of the HIV viral integrase enzyme, preventing the insertion of the viral genome into the host DNA. Dolutegravir is well tolerated, has low to moderate pharmacokinetic (PK) variability, and has sustained antiviral activity when combined with other antiretroviral therapy (ART), without the need for PK boosting, in treatment-naive, treatment-experienced but INSTI-naive, and treatment-experienced and INSTI-resistant adults. 16 Dolutegravir is currently approved at 2 dose levels, 50 mg once daily (for INSTI-naive subjects) and 50 mg twice daily (for INSTI-resistant subjects). Metformin (Glucophage; Bristol-Myers Squibb Company, Princeton, NJ), an antihyperglycemic agent that improves glucose tolerance in subjects with type 2 diabetes mellitus (T2DM) by lowering both basal and postprandial plasma glucose, is considered to be one of the best treatment options for T2DM and has been used for a number of the metabolic comorbidities that are associated with HIV. 7 Under fasting conditions, the absolute bioavailability of a 500 mg metformin immediate release (IR) tablet is approximately 50%60%. 8 Due to its highly hydrophilic nature, metformin is unable to passively diffuse across membranes, and intestinal absorption is paracellular. 9,10 Although metformin can enter enterocytes by apical carrier-facilitated transport mediated primarily by organic cation transporter (OCT) 1 and plasma membrane monoamine transporter (PMAT), enterocytes lack basolateral transporters capable of secreting metformin into blood. Therefore, metformin uptake into enterocytes only enhances intestinal drug retentio Continue reading >>

Population Pharmacokinetics Of Metformin In Healthy Subjects And Patients With Type 2 Diabetes Mellitus: Simulation Of Doses According To Renal Function

Population Pharmacokinetics Of Metformin In Healthy Subjects And Patients With Type 2 Diabetes Mellitus: Simulation Of Doses According To Renal Function

Duong, Janna K ; Kumar, Shaun S ; Kirkpatrick, Carl Michael James ; Greenup, Louise ; Arora, Manit ; Lee, Toong C ; Timmins, Peter ; Graham, Garry G ; Furlong, Timothy J ; Greenfield, Jerry R ; Williams, Kenneth M ; Day, Richard O. / Population pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus: Simulation of doses according to renal function . In: Clinical Pharmacokinetics . 2013 ; Vol. 52. pp. 373 - 384 @article{04f4a3758c18494d816ccb47b20fc901, title = "Population pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus: Simulation of doses according to renal function", abstract = "The population model enabled doses of metformin to be simulated for each stage of renal function, to ensure the concentrations of metformin do not exceed 5 mg/l. However, the plasma concentrations of metformin at these dosage levels are still quite variable and monitoring metformin concentrations may be of value in individualising dosage. This study provides confirmatory data that metformin can be used, with appropriate dosage adjustment, in patients with renal impairment.", author = "Duong, {Janna K} and Kumar, {Shaun S} and Kirkpatrick, {Carl Michael James} and Louise Greenup and Manit Arora and Lee, {Toong C} and Peter Timmins and Graham, {Garry G} and Furlong, {Timothy J} and Greenfield, {Jerry R} and Williams, {Kenneth M} and Day, {Richard O}", Continue reading >>

Clinical Pharmacokinetics Of Metformin

Clinical Pharmacokinetics Of Metformin

, Volume 50, Issue2 , pp 8198 | Cite as Metformin is widely used for the treatment of type 2 diabetes mellitus. It is a biguanide developed from galegine, a guanidine derivative found in Galega officinalis (French lilac). Chemically, it is a hydrophilic base which exists at physiological pH as the cationic species (>99.9%). Consequently, its passive diffusion through cell membranes should be very limited. The mean SD fractional oral bioavailability (F) of metformin is 55 16%. It is absorbed predominately from the small intestine. Metformin is excreted unchanged in urine. The elimination half-life (t1/2) of metformin during multiple dosages in patients with good renal function is approximately 5 hours. From published data on the pharmacokinetics of metformin, the population mean of its clearances were calculated. The population mean renal clearance (CLR) and apparent total clearance after oral administration (CL/F) of metformin were estimated to be 510 130 mL/min and 1140 330 mL/min, respectively, in healthy subjects and diabetic patients with good renal function. Over a range of renal function, the population mean values of CLR and CL/F of metformin are 4.3 1.5 and 10.7 3.5 times as great, respectively, as the clearance of creatinine (CLCR). AS the CLR and CL/F decrease approximately in proportion to CLCR, the dosage of metformin should be reduced in patients with renal impairment in proportion to the reduced CLCR. The oral absorption, hepatic uptake and renal excretion of metformin are mediated very largely by organic cation transporters (OCTs). An intron variant of OCT1 (single nucleotide polymorphism [SNP] rs622342) has been associated with a decreased effect on blood glucose in heterozygotes and a lack of effect of metformin on plasma glucose in homozygotes. An int Continue reading >>

Select Publications By Professor Kenneth Mapson Williams | Unsw Research

Select Publications By Professor Kenneth Mapson Williams | Unsw Research

Day RO;Williams KM;Graham GG, 2013, 'Urate-lowering therapy: Uricosurics', in Gout, pp. 174 - 189, Day RO;Graham GG;Williams KM, 2013, 'Propionic acid derivative drugs (Profens)', in Encyclopedia of Inflammatory Diseases, Springer-Verlag, Berlin Heidelberg, Bachmeier CJ;Brooks PM;Day RO;Graham GG;Littlejohn GO;Morand E;Pile K;Williams KM, 2005, 'Disease-modifying anti-rheumatic drugs (DMARD)', in Nijkamp FJ;Parnham MJ (ed.), Principles of Immunopharmacology (2nd Ed), edn. 2nd, Birkhauser Verlag, Basel, pp. 511 - 544 Day RO;Quinn DI;March LM;Graham GG;Williams KM, 2000, 'Rheumatoid arthritis. New Frontiers in pathogenesis and treatment', in NSAIDs and analgesics, edn. Original, Oxford University Press, Oxford, England, pp. 307 - 328 Bachmeier CJ;Handel ML;Conaghan PG;Williams KM;Graham GG;Brooks PM;Day RO, 1999, 'Disease-modifying antirheumatic drugs', in Nijkamp FP;Parnham MJ (ed.), Principles of Immunopharmacology, edn. 3, Birkhauser Verlag (Springer), Basel, Switzerland, pp. 379 - 403 Graham GG;Milligan MK;Day RO;Williams KM;Ziegler JB, 1998, 'Therapeutic considerations from pharmacokinetics and metabolism: Ibuprofen and paracetamol', in Rainsford KD;Powanda MC (ed.), SAFETY AND EFFICACY OF NON-PRESCRIPTION (OTC) ANALGESICS AND NSAIDS, SPRINGER, SAN FRANCISCO, CA, pp. 77 - 92, Conaghan PG;Lehmann T;Brooks P, 1997, 'Disease-modifying antirheumatic drugs', in Current Opinion in Rheumatology, edn. 3, pp. 183 - 190, Graham GG;Milligan MK;Day RO;Williams KM;Zeig, 1997, 'Therapeutic considerations from pharmacokinetics and metabolism: ibuprofen and paracetamol', in In: `Safety and efficacy of non-prescription (OTC) analgesics, edn. Original, Kluwer Academic Publishers, Great Britain, pp. 77 - 92 Vesey G;Ashbolt NJ;Wallner G;Dorsch R;Williams KM;Veal DA, 1995, 'Assessing cr Continue reading >>

Bioequivalence And Pharmacokinetic Comparison Of Two Metforminimmediate-release Formulations In Healthy Volunteers Under Fedconditions

Bioequivalence And Pharmacokinetic Comparison Of Two Metforminimmediate-release Formulations In Healthy Volunteers Under Fedconditions

Received Date: April 10, 2015; Accepted Date: May 14, 2015; Published Date: May 21, 2015 Citation: Mak WY, Tan SS, Wong JW, Chin SK, Lim AB, et al. (2015) Bioequivalence and Pharmacokinetic Comparison of Two Metformin Immediaterelease Formulations in Healthy Volunteers under Fed Conditions. J Bioequiv Availab 7:184-188. doi: 10.4172/jbb.1000236 Copyright: 2015 Mak WY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Type-2 diabetes mellitus is a common metabolic disorder in Malaysia, where metformin is used as the first-line treatment. Since metformin absorption is altered when administered with food, the US FDA guidance on metformin hydrochloride recommended to conduct bioequivalence study in both fasting and fed conditions. In this study, we intended to establish bioequivalence between a locally manufactured metformin formulation with a reference formulation under fed condition. Methods: The study was a single-dose, open label, randomised, two treatments, two periods, cross-over study in 24 healthy volunteers. The washout period was 7 days to allow adequate time for drug elimination from the body. Analysis of plasma metformin concentration was conducted with a validated reverse-phase HPLC with ultraviolet detection procedure. Non-compartmental modal was used to analyse the pharmacokinetic parameters. Tolerability of both formulations was assessed throughout the study. Results: A total of 24 volunteers were recruited, only 21 had completed the study. Two volunteers dropped out of the study due to personal reason. The third volunteer experienced emesis within 4 hour Continue reading >>

(pdf) Clinical Pharmacokinetics Of Metformin

(pdf) Clinical Pharmacokinetics Of Metformin

1 Departments of Pharmacology &Toxicology and Medicine, St Vincents Clinical School, University of New South Wales, 2 Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide, South Australia, Australia 3 Department of Nephrology, St Vincents Hospital, Sydney, New South Wales, Australia 4 Department of Endocrinology and Diabetes Centre, St Vincents Hospital and Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia 5 School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia 6 Biopharmaceutics Research and Development, Bristol-Myers Squibb Company, Moreton, UK 4.3 Transporters and Absorption of Oral Metformin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 4.4 Concentrations of Metformin in the Small Intestine: Relevance to Action of Metformin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 5. Distribution....................................................................................................... 87 5.1 Transporters and Uptake by Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 5.2 Organic Cation Transporters and Uptake of Metformin by Skeletal Muscle and Heart. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 5.3 Uptake into Erythrocytes: Possible Value in Monitoring Dosage of Metformin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 5.4 Transport and Pharmacokinetics during Pregnancy and Lactation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Continue reading >>

The Pharmacokinetics Of Metformin And Concentrations Of Haemoglobin A1c And Lactate In Indigenous And Non-indigenous Australians With Type 2 Diabetes Mellitus

The Pharmacokinetics Of Metformin And Concentrations Of Haemoglobin A1c And Lactate In Indigenous And Non-indigenous Australians With Type 2 Diabetes Mellitus

The pharmacokinetics of metformin and concentrations of haemoglobin A1C and lactate in Indigenous and non-Indigenous Australians with type 2 diabetes mellitus 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 5Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia 6Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 1School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia 2Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia 3Department of Nephrology, St Vincent's Hospital, Darlinghurst, NSW, Australia 4Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia 5Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia 6Diabetes and Obesity Research Program, Garvan Inst Continue reading >>

Mechanism Of Metformin: A Tale Of Two Sites

Mechanism Of Metformin: A Tale Of Two Sites

Metformin (dimethylbiguanide) features as a current first-line pharmacological treatment for type 2 diabetes (T2D) in almost all guidelines and recommendations worldwide. It has been known that the antihyperglycemic effect of metformin is mainly due to the inhibition of hepatic glucose output, and therefore, the liver is presumably the primary site of metformin function. However, in this issue of Diabetes Care, Fineman and colleagues (1) demonstrate surprising results from their clinical trials that suggest the primary effect of metformin resides in the human gut. Metformin is an orally administered drug used for lowering blood glucose concentrations in patients with T2D, particularly in those overweight and obese as well as those with normal renal function. Pharmacologically, metformin belongs to the biguanide class of antidiabetes drugs. The history of biguanides can be traced from the use of Galega officinalis (commonly known as galega) for treating diabetes in medieval Europe (2). Guanidine, the active component of galega, is the parent compound used to synthesize the biguanides. Among three main biguanides introduced for diabetes therapy in late 1950s, metformin (Fig. 1A) has a superior safety profile and is well tolerated. The other two biguanides, phenformin and buformin, were withdrawn in the early 1970s due to the risk of lactic acidosis and increased cardiac mortality. The incidence of lactic acidosis with metformin at therapeutic doses is rare (less than three cases per 100,000 patient-years) and is not greater than with nonmetformin therapies (3). Major clinical advantages of metformin include specific reduction of hepatic glucose output, with subsequent improvement of peripheral insulin sensitivity, and remarkable cardiovascular safety, but without increasi Continue reading >>

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An Error Occurred Setting Your User Cookie

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