Metformin doses to ensure efficacy and safety in patients with reduced kidney function

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regre...

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Published inPloS one Vol. 16; no. 2; p. e0246247
Main Authors Kuan, Isabelle H. S., Wilson, Luke C., Leishman, Jed C., Cosgrove, Samuel, Walker, Robert J., Putt, Tracey L., Schollum, John B. W., Wright, Daniel F. B.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 18.02.2021
Public Library of Science (PLoS)
Subjects
Acidosis
Adult
Aged
Antidiabetics
Bioavailability
Biology and Life Sciences
Collaboration
Creatinine
Diabetes
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Dosage
Dosage and administration
Drug Dosage Calculations
Drug dosages
Drug therapy
Epidemiology
Epidermal growth factor receptors
Evaluation
Female
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - therapeutic use
Kidney diseases
Kidney Diseases - complications
Kidney Function Tests
Kidneys
Lower bounds
Male
Medicine
Medicine and Health Sciences
Metformin
Metformin - administration & dosage
Metformin - adverse effects
Metformin - pharmacokinetics
Metformin - therapeutic use
Middle Aged
Patients
Pharmacokinetics
Pharmacy
Plasma
Practice guidelines (Medicine)
Quantitative analysis
Research and Analysis Methods
Simulation
Young Adult
Europe
New Zealand
Online AccessGet full text

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Abstract We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r 2 = 0.699), MDRD (r 2 = 0.717) and CKD-Epi (r 2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
AbstractList We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r 2 = 0.699), MDRD (r 2 = 0.717) and CKD-Epi (r 2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r.sup.2 = 0.699), MDRD (r.sup.2 = 0.717) and CKD-Epi (r.sup.2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
An important component of this is the use of the patients’ estimated kidney function to aid dose prediction. [...]a pragmatic guideline must also provide dosing based on different kidney function metrics that might be encountered clinically, including the commonly used creatinine-based equations; Cockcroft and Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-Epi) Collaboration [19–21]. Predicted dose bands for metformin based on kidney function metrics Details of the methods used to determine kidney function metrics including; creatinine clearance using the Cockcroft and Gault equation (CLcrCG) [19], and, eGFR calculated using both the 4-variable MDRD equation (eGFRMDRD) [20] and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKDEPI) [21] are provided in the Supporting Information (S3 File). CLcr is not scaled to BSA. [...]for this analysis metformin clearance estimates were scaled to a BSA of 1.73m2 for comparison with eGFRMDRD and eGFRCKDEPI but were left unscaled for the comparison with CLcr. The daily maintenance dose range for each kidney function band was determined from the predicted metformin CL/Fpredicted/1.73m2 and CL/Fpredicted values as follows; (3)(4) Where Css,ave (target) is the target steady-state average plasma concentration for metformin, CL/Fupper and CL/Flower are the predicted CL/Fpredicted/1.73m2 and CL/Fpredicted values for metformin at the upper or lower bound of the kidney function band.
We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
An important component of this is the use of the patients’ estimated kidney function to aid dose prediction. [...]a pragmatic guideline must also provide dosing based on different kidney function metrics that might be encountered clinically, including the commonly used creatinine-based equations; Cockcroft and Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-Epi) Collaboration [19–21]. Predicted dose bands for metformin based on kidney function metrics Details of the methods used to determine kidney function metrics including; creatinine clearance using the Cockcroft and Gault equation (CLcrCG) [19], and, eGFR calculated using both the 4-variable MDRD equation (eGFRMDRD) [20] and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKDEPI) [21] are provided in the Supporting Information (S3 File). CLcr is not scaled to BSA. [...]for this analysis metformin clearance estimates were scaled to a BSA of 1.73m2 for comparison with eGFRMDRD and eGFRCKDEPI but were left unscaled for the comparison with CLcr. The daily maintenance dose range for each kidney function band was determined from the predicted metformin CL/Fpredicted/1.73m2 and CL/Fpredicted values as follows; (3)(4) Where Css,ave (target) is the target steady-state average plasma concentration for metformin, CL/Fupper and CL/Flower are the predicted CL/Fpredicted/1.73m2 and CL/Fpredicted values for metformin at the upper or lower bound of the kidney function band.
Audience Academic
Author Schollum, John B. W.
Cosgrove, Samuel
Leishman, Jed C.
Putt, Tracey L.
Wright, Daniel F. B.
Walker, Robert J.
Wilson, Luke C.
Kuan, Isabelle H. S.
AuthorAffiliation 2 Department of Medicine, University of Otago, Dunedin, New Zealand
1 School of Pharmacy, University of Otago, Dunedin, New Zealand
University of Liège, BELGIUM
AuthorAffiliation_xml – name: 2 Department of Medicine, University of Otago, Dunedin, New Zealand
– name: 1 School of Pharmacy, University of Otago, Dunedin, New Zealand
– name: University of Liège, BELGIUM
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  givenname: Isabelle H. S.
  orcidid: 0000-0003-3186-8040
  surname: Kuan
  fullname: Kuan, Isabelle H. S.
– sequence: 2
  givenname: Luke C.
  surname: Wilson
  fullname: Wilson, Luke C.
– sequence: 3
  givenname: Jed C.
  surname: Leishman
  fullname: Leishman, Jed C.
– sequence: 4
  givenname: Samuel
  surname: Cosgrove
  fullname: Cosgrove, Samuel
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  orcidid: 0000-0003-3366-0956
  surname: Walker
  fullname: Walker, Robert J.
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  givenname: Tracey L.
  surname: Putt
  fullname: Putt, Tracey L.
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  givenname: John B. W.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33600406$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1046/j.1365-2796.2003.01271.x
10.1016/S0140-6736(98)07037-8
10.2165/11534750-000000000-00000
10.7326/0003-4819-150-9-200905050-00006
10.1038/sj.ijo.0803695
10.2165/00003088-199630050-00003
10.2165/11588310-000000000-00000
10.1007/s40262-015-0323-x
10.2337/dc17-2231
10.1111/j.1365-2125.1996.tb00017.x
10.1007/s00228-017-2251-1
10.1111/j.1365-2125.1981.tb01206.x
10.1111/dme.13098
10.1111/apt.15635
10.1016/j.ekir.2017.03.005
10.1111/dom.12974
10.1159/000180580
10.2337/diacare.18.6.779
10.1002/dmr.5610110509
10.1046/j.1463-1326.2003.00241.x
10.7326/0003-4819-145-4-200608150-00004
10.1007/s40264-019-00854-x
10.1007/s40262-013-0046-9
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2021 Kuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2021 Kuan et al 2021 Kuan et al
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References (pone.0246247.ref022) 2013; 3
A Golay (pone.0246247.ref001) 2008; 32
NC Sambol (pone.0246247.ref027) 1996; 42
IHS Kuan (pone.0246247.ref005) 2019; 42
AM Dissanayake (pone.0246247.ref013) 2017; 2
JD Lalau (pone.0246247.ref010) 2018; 41
IHS Kuan (pone.0246247.ref014) 2020
D Boucaud-Maitre (pone.0246247.ref017) 2016; 33
JD Lalau (pone.0246247.ref023) 1995; 18
Y Bennis (pone.0246247.ref028) 2020
IW Campbell (pone.0246247.ref002) 1995; 11
FC Smith (pone.0246247.ref018) 2020; 51
JD Lalau (pone.0246247.ref025) 2011; 31
AS Levey (pone.0246247.ref021) 2009; 150
UK Prospective Diabetes Study (UKPDS) Group (pone.0246247.ref003) 1998; 352
AS Levey (pone.0246247.ref020) 2006; 145
GG Graham (pone.0246247.ref004) 2011; 50
AME Stades (pone.0246247.ref006) 2004; 255
JD Lalau (pone.0246247.ref029) 2017; 19
JK Duong (pone.0246247.ref008) 2017; 73
JD Lalau (pone.0246247.ref016) 2003; 5
pone.0246247.ref012
pone.0246247.ref011
F Kajbaf (pone.0246247.ref015) 2016; 55
DW Cockcroft (pone.0246247.ref019) 1976; 16
AJ Scheen (pone.0246247.ref024) 1996; 30
GT Tucker (pone.0246247.ref026) 1981; 12
JK Duong (pone.0246247.ref009) 2013; 52
SR Salpeter (pone.0246247.ref007) 2010
References_xml – volume: 255
  start-page: 179
  year: 2004
  ident: pone.0246247.ref006
  article-title: Metformin and lactic acidosis: Cause or coincidence? A review of case reports
  publication-title: J Intern Med
  doi: 10.1046/j.1365-2796.2003.01271.x
– volume: 352
  start-page: 854
  issue: 9131
  year: 1998
  ident: pone.0246247.ref003
  article-title: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
  publication-title: Lancet
  doi: 10.1016/S0140-6736(98)07037-8
– volume: 50
  start-page: 81
  year: 2011
  ident: pone.0246247.ref004
  article-title: Clinical pharmacokinetics of metformin.
  publication-title: Clin Pharmacokinet
  doi: 10.2165/11534750-000000000-00000
– volume: 150
  start-page: 604
  year: 2009
  ident: pone.0246247.ref021
  article-title: A new equation to estimate glomerular filtration rate
  publication-title: Ann Intern Med
  doi: 10.7326/0003-4819-150-9-200905050-00006
– volume: 32
  start-page: 61
  year: 2008
  ident: pone.0246247.ref001
  article-title: Metformin and body weight
  publication-title: Int J Obes
  doi: 10.1038/sj.ijo.0803695
– ident: pone.0246247.ref011
– volume: 30
  start-page: 359
  year: 1996
  ident: pone.0246247.ref024
  article-title: Clinical pharmacokinetics of metformin
  publication-title: Clin Pharmacokinet
  doi: 10.2165/00003088-199630050-00003
– volume: 31
  start-page: 435
  year: 2011
  ident: pone.0246247.ref025
  article-title: Establishment of a database of metformin plasma concentrations and erythrocyte levels in normal and emergency situations
  publication-title: Clin Drug Investig
  doi: 10.2165/11588310-000000000-00000
– volume: 55
  start-page: 439
  year: 2016
  ident: pone.0246247.ref015
  article-title: Therapeutic Concentrations of Metformin: A Systematic Review
  publication-title: Clin Pharmacokinet
  doi: 10.1007/s40262-015-0323-x
– volume: 41
  start-page: 547
  year: 2018
  ident: pone.0246247.ref010
  article-title: Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4
  publication-title: Diabetes Care
  doi: 10.2337/dc17-2231
– volume: 42
  start-page: 510
  year: 1996
  ident: pone.0246247.ref027
  article-title: Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HCl in man
  publication-title: Br J Clin Pharmacol
  doi: 10.1111/j.1365-2125.1996.tb00017.x
– volume: 73
  start-page: 981
  year: 2017
  ident: pone.0246247.ref008
  article-title: A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function
  publication-title: Eur J Clin Pharmacol
  doi: 10.1007/s00228-017-2251-1
– volume: 12
  start-page: 235
  year: 1981
  ident: pone.0246247.ref026
  article-title: Metformin kinetics in healthy subjects and in patients with diabetes mellitus
  publication-title: Br J Clin Pharmacol
  doi: 10.1111/j.1365-2125.1981.tb01206.x
– volume: 33
  start-page: 1536
  year: 2016
  ident: pone.0246247.ref017
  article-title: Lactic acidosis: relationship between metformin levels, lactate concentration and mortality
  publication-title: Diabet Med
  doi: 10.1111/dme.13098
– volume: 51
  start-page: 565
  year: 2020
  ident: pone.0246247.ref018
  article-title: The safety and pharmacokinetics of metformin in patients with chronic liver disease
  publication-title: Aliment Pharmacol Ther
  doi: 10.1111/apt.15635
– volume: 3
  start-page: 1
  year: 2013
  ident: pone.0246247.ref022
  article-title: KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
  publication-title: Kidney Int (Supplements)
– volume: 2
  start-page: 705
  year: 2017
  ident: pone.0246247.ref013
  article-title: Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy
  publication-title: Kidney Int Rep
  doi: 10.1016/j.ekir.2017.03.005
– volume: 19
  start-page: 1502
  year: 2017
  ident: pone.0246247.ref029
  article-title: Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm
  publication-title: Diabetes Obes Metab
  doi: 10.1111/dom.12974
– volume: 16
  start-page: 31
  year: 1976
  ident: pone.0246247.ref019
  article-title: Prediction of creatinine clearance from serum creatinine
  publication-title: Nephron
  doi: 10.1159/000180580
– ident: pone.0246247.ref012
– year: 2020
  ident: pone.0246247.ref014
  article-title: Understanding the association between metformin plasma concentrations and lactate
  publication-title: Br J Clin Pharmacol
– volume: 18
  start-page: 779
  year: 1995
  ident: pone.0246247.ref023
  article-title: Role of metformin accumulation in metformin-associated lactic acidosis
  publication-title: Diabetes Care
  doi: 10.2337/diacare.18.6.779
– start-page: CD002967
  issue: 1
  year: 2010
  ident: pone.0246247.ref007
  article-title: Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus
  publication-title: Cochrane Database Syst Rev
– volume: 11
  start-page: S57
  issue: Supp 1
  year: 1995
  ident: pone.0246247.ref002
  article-title: Worldwide experience of metformin as an effective glucose-lowering agent: a meta-analysis
  publication-title: Diabetes Metab Revi
  doi: 10.1002/dmr.5610110509
– volume: 5
  start-page: 93
  year: 2003
  ident: pone.0246247.ref016
  article-title: Measurement of metformin concentration in erythrocytes: clinical implications
  publication-title: Diabetes Obes Metab
  doi: 10.1046/j.1463-1326.2003.00241.x
– volume: 145
  start-page: 247
  year: 2006
  ident: pone.0246247.ref020
  article-title: Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate
  publication-title: Ann Intern Med
  doi: 10.7326/0003-4819-145-4-200608150-00004
– volume: 42
  start-page: 1449
  year: 2019
  ident: pone.0246247.ref005
  article-title: The association between metformin therapy and lactic acidosis
  publication-title: Drug Saf
  doi: 10.1007/s40264-019-00854-x
– year: 2020
  ident: pone.0246247.ref028
  article-title: A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context
  publication-title: Crit Care Med
– volume: 52
  start-page: 373
  year: 2013
  ident: pone.0246247.ref009
  article-title: Population pharmacokinetics of metformin in healthy subjects and patients with type 2 diabetes mellitus: simulation of doses according to renal function
  publication-title: Clin Pharmacokinet
  doi: 10.1007/s40262-013-0046-9
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Snippet We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies...
An important component of this is the use of the patients’ estimated kidney function to aid dose prediction. [...]a pragmatic guideline must also provide...
An important component of this is the use of the patients’ estimated kidney function to aid dose prediction. [...]a pragmatic guideline must also provide...
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SubjectTerms Acidosis
Adult
Aged
Antidiabetics
Bioavailability
Biology and Life Sciences
Collaboration
Creatinine
Diabetes
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Dosage
Dosage and administration
Drug Dosage Calculations
Drug dosages
Drug therapy
Epidemiology
Epidermal growth factor receptors
Evaluation
Female
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - therapeutic use
Kidney diseases
Kidney Diseases - complications
Kidney Function Tests
Kidneys
Lower bounds
Male
Medicine
Medicine and Health Sciences
Metformin
Metformin - administration & dosage
Metformin - adverse effects
Metformin - pharmacokinetics
Metformin - therapeutic use
Middle Aged
Patients
Pharmacokinetics
Pharmacy
Plasma
Practice guidelines (Medicine)
Quantitative analysis
Research and Analysis Methods
Simulation
Young Adult
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Title Metformin doses to ensure efficacy and safety in patients with reduced kidney function
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