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Oral anti-diabetic drugs and their use in chronic kidney disease according to drug technical data sheets
Citations
Objectives
To evaluate the level of concordance between the 2007 PRETEMED guidelines and the 2012 American College of Chest Physicians (ACCP) guidelines in medical patients at admission.
Methods
A cross-sectional, observational and descriptive study was designed and included all adult medical patients admitted from an emergency department. Firstly, patients classified as low-moderate risk and high risk according to PRETEMED were compared to those classified by ACCP as low and high risk. Secondly, the same analysis was performed but this time low and moderate-high risk patients according to PRETEMED were compared to ACCP low and high risk patients. The level of concordance was calculated using the kappa concordance index. The study was approved by the Ethics Committee for Clinical Research of the hospital.
Results
The analysis was performed with 207 patients; 53.1% were male and the median age was 75.3 years (minimum 18, maximum 100 years old). The most common diagnosis at admission was related to a respiratory disease (37.2%). The level of concordance was 0.59 (95% CI 0.48 to 0.70) when moderate risk patients were grouped with low-risk patients and 0.53 (95% CI 0.42 to 0.65) when moderate risk patients were grouped with high-risk patients.
Conclusions
The level of concordance between both guides is moderate. It would be helpful to confirm whether the level of agreement improves when the patient's condition stabilises after several days of hospitalisation.
Unlabelled:
Albiglutide is a glucagon-like peptide-1 analogue composed of tandem copies of modified human glucagon-like peptide-1 (7-36) coupled to recombinant human albumin that is approved in adults for the treatment of type 2 diabetes mellitus. After subcutaneous administration, albiglutide is likely primarily absorbed via the lymphatic circulation, with maximum concentrations being reached in 3 to 5 days; steady-state exposures are achieved following approximately 4 to 5 weeks of once-weekly administration. The elimination half-life of albiglutide is approximately 5 days. Clearance of albiglutide is 67 mL/h with between-subject variability of 34.9%; no covariates have been identified that would require dose adjustment of albiglutide. Albiglutide lowers the fasting plasma glucose and reduces postprandial glucose excursions. In addition, β-cell secretion is enhanced by albiglutide during hyperglycemia, whereas secretion is suppressed during hypoglycemia; α-cell response to hypoglycemia is not impaired by albiglutide. Albiglutide does not prolong the corrected QT interval but has a modest effect on heart rate in patients with type 2 diabetes mellitus. Dose adjustment is not suggested in patients with renal impairment, but experience in patients with severe renal impairment is very limited, and it is recommended that albiglutide be used with care in such patients due to an increased frequency of diarrhea, nausea, and vomiting. No clinically relevant drug interactions have been observed in clinical trials.
Trial registration:
NCT00938158, NCT01406262, NCT00537719, NCT01077505, NCT01147731, NCT01147718, NCT01147692, NCT00354536, NCT00394030, NCT00530309, NCT01357889, NCT00518115, NCT01098461, NCT01475734, NCT00849017, NCT00838916, NCT00839527, NCT01098539.
Type 2 diabetes mellitus is a complex disease that is frequently associated with a constellation of risk factors that contribute to worsening morbidity and mortality in affected individuals. To increase quality of life in these persons, both hyperglycemia and other risk factors need to be considered. The first step is probably to establish the glycemic targets for each patient at each stage of the disease. Currently, clinical practice guidelines recommend individualizing glycemic targets with HbA1c values that range from 6-8.5%, depending on the patient's characteristics. Nine different antidiabetic drug families are available, each with distinct characteristics, thus allowing multiple combinations to aid the individual approach to hyperglycemia in each patient at each time point. There are numerous treatment algorithms that aim to simplify and summarize the various therapeutic possibilities. However, with some exceptions, these algorithms do not take into account the individual characteristics of each patient and are excessively general. To select the most appropriate drug for each patient at distinct moments, it is essential to evaluate the patient's comorbidities, such as heart failure, frailty, and the risk of hypoglycemias.
Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.
Background:
Chronic kidney disease is frequently present in patients with type 2 diabetes mellitus (T2DM). New therapeutic options in this patient subpopulation are needed.
Objectives:
Assess the effect of renal impairment on the pharmacokinetics (PK), efficacy, and safety of albiglutide in single- and multiple-dose studies.
Methods:
Pharmacokinetics, safety, and efficacy of once weekly albiglutide in patients with T2DM was assessed from a single-dose (30 mg), nonrandomized, open-label study (N = 41) including subjects with normal and varying degrees of renal impairment, including hemodialysis, and a pooled analysis of 4 phase 3, randomized, double-blind (1 open-label), active or placebo-controlled multiple-dose studies. The pooled analysis of the latter 4 studies (N = 1113) was part of the population PK analysis, which included subjects with normal and varying degrees of renal impairment (mild, moderate, severe) treated with albiglutide (30 to 50 mg) to primary end points of 26 to 52 weeks.
Results:
Single-dose PK showed area-under-the-curve ratios (and 90% CIs) of 1.32 (0.96-1.80), 1.39 (1.03-1.89), and 0.99 (0.63-1.57) for the moderate, severe, and hemodialysis groups, respectively, relative to the normal group. Results indicate that modest increases in plasma concentration of albiglutide were observed with the severity of renal impairment. There was a trend for more glycemic lowering as the estimated glomerular filtration rate decreased. The severe group had a higher frequency of gastrointestinal (eg, diarrhea, constipation, nausea, and vomiting) and hypoglycemic (with background sulfonylurea use) events compared with patients with mild or moderate renal impairment.
Conclusion:
The PK, efficacy, and safety data indicate that albiglutide has a favorable benefit/risk ratio in patients with T2DM and varying degrees of renal impairment, and the need for a dose adjustment is not suggested. Experience in patients with more severe renal impairment is very limited, so the recommendation is to use albiglutide carefully in this population.
Clinical trial registration:
(ClinicalTrials.gov):NCT00938158, NCT00849017, NCT00838916, NCT00839527, NCT0198539.
We compared and contrasted guidelines on metformin treatment in patients with chronic kidney disease (CKD) around the world, with the aim of helping physicians to refine their analysis of the available evidence before deciding whether to continue or withdraw this drug.
We performed a systematic research for metformin contraindications in: (i) official documents from the world's 20 most populated countries and the 20 most scientifically productive countries in the field of diabetology and (ii) publications referenced in electronic databases from 1990 onwards.
We identified three international guidelines, 31 national guidelines, and 20 proposals in the scientific literature. The criteria for metformin withdrawal were (i) mainly qualitative in the most populated countries; (ii) mainly quantitative in the most scientifically productive countries (with, in all cases, a suggested threshold for withdrawing metformin); and (iii) quantitative in all, but one of the literature proposals, with a threshold for withdrawal in most cases (n = 17) and/or adjustment of the metformin dose as a function of renal status (n = 8). There was a good degree of consensus on serum creatinine thresholds; whereas guidelines based on estimated glomerular filtration rate thresholds varied from 60 mL/minute/1.73 m(2) up to stage 5 CKD. Only one of the proposals has been tested in a prospective study.
In general, proposals for continuing or stopping metformin therapy in CKD involve a threshold (whether based on serum creatinine or estimated glomerular filtration rate) rather than the dose adjustment as a function of renal status (in stable patients) performed for other drugs excreted by the kidney. Copyright © 2013 John Wiley & Sons, Ltd.
Nefrologia 2012;32(6):838-9. doi: 10.3265/Nefrologia.pre2012.Oct.11783. Reply to: Del Pozo et al. Comment on Nefrologia 2012;32(6):837. Nefrologia 2012; 32(4):419-26.
Nefrologia 2012;32(6):835-7. doi: 10.3265/Nefrologia.pre2012.Oct.11731. Reply to: Serra Tarragon. Comment on Nefrologia 2012;32(6):835. Nefrologia 2012; 32(4):419-26.
