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      Discrepancias entre documentos de consenso, guías, práctica clínica y normativa legal en el tratamiento de los pacientes con diabetes mellitus tipo 2 Translated title: Discrepancies among consensus documents, guidelines, clinical practice and the legal framework for the treatment of type 2 diabetes mellitus patients

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          Abstract

          Reflexionamos sobre las discrepancias encontradas en el uso generalizado de metformina en pacientes con diabetes mellitus tipo 2, la ausencia de criterios uniformes acerca de su indicación en los diferentes estadios de insuficiencia renal y sobre su empleo en estos pacientes. Realizamos un corte transversal en 304 pacientes diabéticos tipo 2, visitados a lo largo de 2010 de forma consecutiva en consulta de Atención Primaria, Endocrinología y Nefrología, con una tasa de filtrado glomerular (TFG) estimada < 60 ml/min/1,73 m² y tratados con antidiabéticos orales (ADO). Revisamos la frecuencia de uso de metformina y otros antidiabéticos en función del tipo de consulta y el grado de función renal. El ADO más utilizado fue metformina (54,9%), seguido de repaglinida (47,7%), dipeptidil-peptidasa (IDPP-4) (28,6%) y sulfonilureas (18,4%). Observamos menor uso de metformina y mayor de repaglinida, estadísticamente significativo, en pacientes de Nefrología, y mayor de IDPP-4 en Atención Primaria. La metformina fue la menos utilizada, con TFG entre 29-15 ml/min/1,73 m² (13,3%), junto con las sulfonilureas, y la más prescrita en TFG mayores (70,0% con 59-45 ml/min/1,73 m²), p < 0,001. La repaglinida fue más utilizada, con TFG entre 29-15 ml/min/1,73 m² (76,7%), mientras que se prescribió menos con TFG mayores (38,9% con 59-45 ml/min/1,73 m²), p < 0,001. En nuestra opinión, en la literatura existen evidencias sobre el uso de metformina en pacientes con TFG entre 30-60 ml/min/1,73 m² que permiten sugerir su empleo con precaución en este grupo de pacientes y, algo que es importante para la práctica médica, hacerlo dentro de un marco legal.

          Translated abstract

          In this paper we analyse the discrepancies that exist in the widespread prescription of metformin in patients with type 2 diabetes and the lack of guidelines concerning its prescription in the different stages of renal failure. This cross-sectional study includes 304 patients with type 2 diabetes treated with oral antidiabetic drugs (ADOs) and a glomerular filtration rate (estimated GFR) <60ml/min/1.73m². Patients were attended in consecutive visits to primary health centres or in hospital departments of endocrinology or nephrology during 2010. We studied the frequency of metformin and other ADO prescriptions according to renal function and the department in which the patient was treated. The ADO most frequently prescribed was metformin (54.9%), followed by repaglinide (47.7%), DPP4 inhibitors (28.6%), and sulfonylureas (18.4%). However, in nephrology departments, repaglinide was more frequently prescribed than metformin (P<.001), whereas in primary health centres, the prescription of DPP4 inhibitors increased. In patients with an estimated GFR of 15-29ml/min/1.73m², metformin (13.3%) and sulfonylureas were the least prescribed, whereas metformin was much more frequently prescribed (70.0%) when estimated GFR was 45-59ml/min/1.73m² (P<.001). In contrast, patients with an estimated GFR of 15-29ml/min/1.73m² were mainly prescribed repaglinide (76.7%), as opposed to patients with an estimated GFR of 45-59ml/min/1.73m² (38.9%) (P<.001). Substantial evidence suggests that the recommendations for the use of ADO should be modified. This would lead to safely prescribing ADO in patients with an estimated GFR<60ml/min/1.73m², and more importantly in medical practice, according to the law.

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          Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2.

          The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics. Test of diagnostic accuracy. Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index. eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine. Measured GFR using urinary or plasma clearance of exogenous filtration markers. Mean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR or=90 mL/min/1.73 m2. Limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation. Copyright (c) 2010 National Kidney Foundation, Inc. All rights reserved.
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            Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus.

            As newer oral diabetes agents continue to emerge on the market, comparative evidence is urgently required to guide appropriate therapy. To summarize the English-language literature on the benefits and harms of oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, meglitinides, and alpha-glucosidase inhibitors) in the treatment of adults with type 2 diabetes mellitus. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception through January 2006 for original articles and through November 2005 for systematic reviews. Unpublished U.S. Food and Drug Administration and industry data were also searched. 216 controlled trials and cohort studies and 2 systematic reviews that addressed benefits and harms of oral diabetes drug classes available in the United States. Using standardized protocols, 2 reviewers serially abstracted data for each article. Evidence from clinical trials was inconclusive on major clinical end points, such as cardiovascular mortality. Therefore, the review was limited mainly to studies of intermediate end points. Most oral agents (thiazolidinediones, metformin, and repaglinide) improved glycemic control to the same degree as sulfonylureas (absolute decrease in hemoglobin A1c level of about 1 percentage point). Nateglinide and alpha-glucosidase inhibitors may have slightly weaker effects, on the basis of indirect comparisons of placebo-controlled trials. Thiazolidinediones were the only class that had a beneficial effect on high-density lipoprotein cholesterol levels (mean relative increase, 0.08 to 0.13 mmol/L [3 to 5 mg/dL]) but a harmful effect on low-density lipoprotein (LDL) cholesterol levels (mean relative increase, 0.26 mmol/L [10 mg/dL]) compared with other oral agents. Metformin decreased LDL cholesterol levels by about 0.26 mmol/L (10 mg/dL), whereas other oral agents had no obvious effects on LDL cholesterol levels. Most agents other than metformin increased body weight by 1 to 5 kg. Sulfonylureas and repaglinide were associated with greater risk for hypoglycemia, thiazolidinediones with greater risk for heart failure, and metformin with greater risk for gastrointestinal problems compared with other oral agents. Lactic acidosis was no more common in metformin recipients without comorbid conditions than in recipients of other oral diabetes agents. Data on major clinical end points were limited. Studies inconsistently reported adverse events other than hypoglycemia, and definitions of adverse events varied across studies. Some harms not assessed in trials or observational studies may have been overlooked. Compared with newer, more expensive agents (thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides), older agents (second-generation sulfonylureas and metformin) have similar or superior effects on glycemic control, lipids, and other intermediate end points. Large, long-term comparative studies are needed to determine the comparative effects of oral diabetes agents on hard clinical end points.
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              Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

              OBJECTIVE—Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS—This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time. RESULTS—Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use. CONCLUSIONS—Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                nefrologia
                Nefrología (Madrid)
                Nefrología (Madr.)
                Sociedad Española de Nefrología (Cantabria, Santander, Spain )
                0211-6995
                1989-2284
                2012
                : 32
                : 3
                : 367-373
                Affiliations
                [03] San Vicente del Raspeig orgnameCentro de Atención Primaria de San Vicente del Raspeig
                [01] Alcoy orgnameHospital Virgen de los Lirios orgdiv1Sección de Nefrología
                [04] Alcoy orgnameHospital Virgen de los Lirios
                [02] Alcoy orgnameHospital Virgen de los Lirios orgdiv1Sección de Endocrinología
                Article
                S0211-69952012000500014
                6cb8639e-887e-48f1-9d8f-b216210e32c7

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

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                Diabetes mellitus tipo 2,Metformina,Documentos de Consenso,Guías,Normativa legal,Insuficiencia renal crónica,Diabetes mellitus,Metformin,Consensus Documents,Guidelines,Legal Framework,Chronic Kidney Disease

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