The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.

Seguridad y eficacia de torasemida en el tratamiento de pacientes con diagnóstico de insuficiencia cardiaca congestiva / Safety and efficacy of torasemide in the treatment of patients diagnosed with congestive heart failure

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso de la seguridad y eficacia de torasemida en el tratamiento de pacientes con diagnóstico de insuficiencia cardiaca congestiva dentro del sistema de EsSalud, indicación actualmente no contemplada en el petitorio de medicamentos. Generalidades: A pesar de los continuos avances en el tratamiento de los pacientes con insuficiencia cardiaca, también llamada insuficiencia cardiaca congestiva (ICC), en las últimas décadas, la casuística de ICC sigue siendo muy importante alrededor del mundo. Sólo en los Estados Unidos se estima que 5.1 millones de adultos padecen de ICC con 825,000 nuevos casos al año, estimándose que para el año 2030 se espera que la prevalencia aumente un 46%, resultando en más de 8 millones de adultos afectados. Tecnología Sanitaria de Interés: Torasemida: Torasemida (torasemide, torsemide) es un diurético de asa que actúa sobre la rama gruesa ascendente del asa de Henle promoviendo una rápida excreción de agua, sodio y cloruro. Como tal fue aprobado por la FDA en agosto de 1993 originalmente como un diurético para el manejo de edema secundario a insuficiencia cardiaca congestiva, insuficiencia renal o enfermedad hepática, así mismo, su uso está aprobado sólo o en combinación con otros agentes antihipertensivos para el manejo de hipertensión. METODOLOGÍA: El protocolo de esta revisión sistemática fue preparado y revisado con el equipo técnico de IETSI. Las siguientes fuentes han sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible que directamente responda a la pregunta PICO de esta evaluación: Medline/Pubmed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Translating Research into Practice (TRIP Database), Institute for Health Technology Assessment Ludwig Boltzmann Gelsellschaft (LBI-HTA) de Austria, American Heart Association (AHA) de los Estados Unidos, American Society of Cardiología (ASC) de los Estados Unidos, European Society of Cardiología (ESC) de Europa, National Guideline Clearinghouse (NCG) de los Estados Unidos, National Institute for Health and Care Excellence (NICE) del Reino Unido National Institute for Health Research (NIHR) del Reino Unido Canadian Agency for Drugs and Technologies in Health (CADTH) Scottish Medicines Consortium (SMC). RESULTADOS: Luego de revisar un total de 485 referencias resultados de nuestra búsqueda bibliográfica, logramos filtrar 98 referencias relevantes para nuestra pregunta PICO de interés (Tabla 1), de los cuales sólo nueve referencias fueron finalmente seleccionadas para nuestro análisis toda vez que constituían referencias que respondían a la pregunta PICO de interés de este dictamen, incluyendo tres guías de práctica clínica, dos meta-análisis, cuatro ensayos clínicos de fase III. CONCLUSIONES: A la fecha no se disponen de evidencias suficientes para recomendar torasemida en comparación con furosemida como una alternativa de tratamiento más eficaz, seguro y costo efectiva en el manejo de pacientes con ICC y clase funcional NYHA III o IV. La evidencia disponible sugiere que torasemida no ofrece mayores beneficios que furosemida en términos de sobrevida, disminución de la clase funcional NYHA, disminución de las tasas de re-hospitalizaciones, mejora de la calidad de vida o disminución de los eventos adversos. De manera aislada algunos estudios dan cuenta de que torasemida puede disminuir las tasas de re-hospitalización y mejorar algunos aspectos de calidad de vida, sin embargo esta evidencia no es consistente con la de otros estudios que no confirman estos hallazgos y lo que es más importante, en general este tipo de evidencias no es extrapolable a la población de interés de este dictamen toda vez que la gran mayoría de participantes por estos estudios fueron enrolados con una clase funcional NYHA II, los menos con una clase funcional NYHA III y sólo en raras ocasiones con una clase funcional NYHA IV. la fecha no se dispone de evidencias que soporten la hipótesis de que torasemida representa una alternativa de tratamiento más costo-efectiva que furosemida en el manejo de los pacientes con ICC. El Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI no aprueba el uso de torasemida como una alternativa a furosemida en el manejo de pacientes con ICC y clases funcionales NYHA III o IV.

Comparative Evaluation of Glycemic Control & Changes in Lipid Profile with Combined Oral Hypoglycemics (A Sulfonylurea Plus Pioglitazone Versus a Sulfonylurea Plus Metformin) in Patients with Type 2 Diabetes Mellitus.

Emerging datas have shown a high failure rate of longterm monotherapy in preventing the vascular complications of DM II. It establishes the significance of meal time hyperglycemia and the role of post-prandial glucose excursions in the development and progression of vascular complications. This prospective, randomized, open parallel group study was conducted on patients selected from those who were attending O.P.D. of Department of Endocrinology and Human Metabolism of SVBP Hospital, L.L.R.M. Medical College, Meerut. The study have demonstrated that the combination therapy with Sulfonylurea plus Pioglitazone (SUP) is an effective regimen for patients who are insufficiently treated with Sulfonylurea mono-therapy. This regimen may provide a possible positive effect on other coronary risk factors/ dyslipidemias associated with the type 2 Diabetes.

Exenatide and acute pancreatitis.

For a female, type 2 diabetic patient, with 4 years duration of diabetes, Exenatide (Byetta) was prescribed as glycaemic control was not satisfactory along with Glimepiride and Metformin. She had gastrointestinal disturbances, since the first day of the injection. From the eighth day she developed signs of acute pancreatitis which was confirmed with CT-Scan and biochemical investigations. Byetta was withdrawn, the patient was treated for acute pancreatitis and the symptoms subsided.

Eficacia de los hipoglicemiantes orales en el control metabólico de pacientes con diabetes mellitus gestacional / Effectiveness of oral hypoglycemic drugs in the metabolic control of patients with gestational diabetes

Gestational Diabetes is characterized by different degrees of glucose intolerance that produce a series of fetal and perinatal alterations. During many years, in those cases of gestational diabetes that did not respond to nutritional interventions, the use of insulin was a proven treatment to achieve metabolic control and thus a better perinatal outcome. At present, some new oral hypoglycemic drugs, from the family of sulfonylureas and biguanides, have been shown to be safe, of low cost, and apparently effective in the metabolic control of this disease. We review the publications that propose the use of oral hypoglycemic drugs for the metabolic control of gestational diabetes that does not respond to nutritional measures.

Simultaneous determination of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage from by RP-HPLC METHOD

A simple, fast, and precise reverse phase, isocratic HPLC method was developed for the separation and quantification of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage form. The quantification was carried out using Inertsil ODS [250 x 4.6 mm, 5micro] column and mobile phase comprised of acetonitrile and ammonium acetate [pH 4.5; 20mM] in proportion of 60:40 [v/v]. The flow rate was 1.0 ml/min and the effluent was monitored at 230 nm. The retention time of pioglitazone and glimepiride were 7.0 +/- 0.1 and 10.2 +/- 0.1 min respectively. The method was validated in terms of linearity, precision, accuracy, and specificity, limit of detection and limit of quantitation. Linearity of pioglitazone and glimepiride were in the range of 2.0 to 200.0microg/ml and 0.5-50microg/ml respectively. The percentage recoveries of both the drugs were 99.85% and 102.06% for pioglitazone and glimepiride respectively from the tablet formulation. The proposed method is suitable for simultaneous determination of pioglitazone and glimepiride in pharmaceutical dosage form and bulk drug

Estudo comparativo da biodisponibilidade relativa de duas formulações de glimepirida em voluntários sadios de ambos os sexos após administração de uma dose única de um comprimido de 4 mg / Comparison study of two glimepiride formulations bioavailability in healthy volunteers of both sexes after a single dose administration

OBJETIVO: Comparar a biodisponibilidade de duas formulações de glimepirida em 26 voluntários sadios de ambos os sexos. MATERIAL E MÉTODOS: O estudo foi aberto, cruzado e randomizado com dois períodos e wash out de 14 dias. As amostras foram obtidas em um intervalo de 48 horas. As concentrações de glimepirida foram analisadas por HPLC MS/MS. Das curvas de concentração de glimepirida no plasma versus tempo, foram obtidos os seguintes parâmetros farmacocinéticos: ASC(0-t), ASC(0-∞), Cmax, Ke, Tmax e T1/2. RESULTADOS: A razão entre as média geométricas de Glimepirida/Amaryl® 4 mg foi de 102,35 por cento para ASC(0-t); 102,35 por cento para ASC(0-∞) e 99,31 por cento para Cmax. Os intervalos de confiança de 90 por cento (IC 90 por cento) foram de 92,62-109,55 por cento; 95,62-109,55 por cento e 88,60-111,32 por cento, respectivamente. CONCLUSÃO: Como o IC 90 por cento para Cmax, ASC(0-t) e ASC(0-∞) estava dentro do intervalo de 80-125 por cento, concluiu-se que ambas as formulações foram bioequivalentes de acordo com o grau e a extensão de sua absorção.

OBJECTIVE: To compare the bioavailability of two glimepiride 4-mg tablet formulation in 26 healthy volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Samples were obtained over a 48-hour interval. Glimepiride concentrations were analyzed by LC-MS-MS. From the glimepiride plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(0-last), AUC(0-t), AUC(0-∞), Ke, T1/2, Cmax, and Tmax. RESULTS: Geometric mean of Glimepirida/Amaryl® 4 mg was 102.35 percent for AUC(0-t), 102.35 percent for AUC(0-∞) and 99.31 percent for Cmax. The 90 percent CI was 92.62-109.55 percent; 95.62-109.55 percent e 88.60-111.32 percent, respectively. CONCLUSION: Since the 90 percent CI for both Cmax, AUC(0-t), and AUC(0-∞) were within the interval of 80-125 percent, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.

Evaluation of efficacy and safety of fixed dose combination of glimepiride 2 mg pluspioglitazone 15 mg plus metformin SR 500 mg in the management of patients with type-2 diabetes mellitus.

An estimated 25 million Indians currently have diabetes and the projections indicate Indians would be the largest group by the year 2025 AD. An open, phase III, multicentric study was conducted to determine the efficacy and tolerability of the triple drug combination glimepiride 2 mg plus pioglitazone hydrochloride 15 mg plus metformin SR 500 mg for 8 weeks in 101 Indian patients with type 2 diabetes mellitus. The study revealed that the triple drug combination could achieve the recommended goals, recommended by American Diabetic Association, for fasting blood glucose < or = 140 mg/dl and glycosylated haemoglobin (HbA1c) of < or = 8%. After 8 weeks, the mean fasting blood glucose (baseline 189.61) was reduced to 111.68 (41% reduction); the mean glycosylated haemoglobin (baseline 10.32) was significantly reduced to 7.54 (26% reduction). The triple drug combination significantly reduced the levels of triglyceride, low density lipoproteins and total cholesterol. These significant levels were achieved within 8 weeks and all patients tolerated the drug well with no reported case of serious adverse events including hypoglycaemia. There were also no reported drug interactions in the study. Since the decrease in HbA1c was continuous and throughout the study, a further decrease in the HbA1c levels would have been noted since the present trial was designed for a period of 8 weeks. Thus, the present study confirms the efficacy and safety of FDC of the triple drug combination in patients with type 2 diabetes.

Immunoreactive insulin response to a single dose of glimepiride in lean type 2 diabetic subjects.

BACKGROUND: The best method for glucose lowering in lean type 2 diabetes remains controversial and this study was undertaken to study the 24 hour insulin response of these diabetics to glimepiride, a sulfonylurea with distinctive properties. METHODS: Twenty five consecutive newly diagnosed diet-unresponsive lean type 2 diabetics (BMI < 19 kg/m2) without any vascular complications were given single dose (1 mg) of glimepiride and insulin responses were measured 2,4,8,12 and 24 hours later. Pre and post-glimepiride blood glucose levels were also measured. RESULTS: All the post-glimepiride insulin levels were significantly higher than basal values. Increase in insulin secretion peaked at four hours and benefits lasted for at least 24 hours. This was accompanied by clinically and statistically significant reductions in fasting and postprandial blood glucose levels. Maximum secretory response correlated positively with beta cell function (HOMA) and negatively with fasting glucose. CONCLUSIONS: Glimepiride improved insulin secretion and hyperglycemia in lean type 2 diabetic subjects, with benefits lasting for 24 hours. The degree of response was proportional to the beta cell reserve, and occurred irrespective of the presence or absence of markers of insulin resistance.

Rational choice of oral antihyperglycaemic agents.

Until 1995 sulphonylureas and metformin formed the mainstay of oral pharmacotherapy of type 2 diabetes mellitus. Since then many new insulin secretagogues and new classes of oral antihyperglycaemic agents have been launched. This has improved the management of type 2 diabetes mellitus. Oral agents available currently in Indian market are: Those predominantly targeting beta cell dysfunction, those predominantly targeting insulin resistance and those inhibit carbohydrate absorption. Strategies for treatment with oral antihyperglycaemic agents are: Targeting fasting hyperglycaemia, targeting postprandial hyperglycaemia, minimising cost therapy, minimising weight gain and minimising patient effort strategies. Special situations where antihyperglycaemic agents used are: Teenage diabetes, elderly diabetes, persons with erratic lifestyle, persons with cardiac disease, renal disease and in pregnancy.

Glimepiride in type 2 diabetes mellitus Thai patients.

This study aimed to confirm the efficacy of glimepiride given once daily in the treatment of Thai type 2 diabetic patients and to find out the optimum dosage for Thai patients. The patients were enrolled at the diabetic clinics of 5 hospitals (Rajavithi, Chulalongkorn, Pramongkutklao, Siriraj and Theptarin Hospitals). All patients started glimepiride 1 mg once daily and escalated to 2, 3, 4 and until 6 mg every 4 weeks if fasting plasma glucose (FPG) exceeded 140 mg/dL. Subjects were 60 females and 29 males with an average age of 52.2 +/- 10.0 years. Mean BMI was 25.5 +/- 3.8 kg/m2. Fifty seven patients (64.0%) were drug naïve and thirty two patients (36.0%) had been previously treated with oral hypoglycemic agents. Seventy three per cent of the drug naïve and 37 per cent of the previously treated patients could be controlled with 1-2 mg of glimepiride once daily. At the twelfth week of treatment, mean fasting plasma glucose decreased from 224.6 to 156.6 mg/dL (30% reduction) and mean HbA1c decreased from 10.0 to 7.5 per cent (25% reduction). At the end of the study 49.4 per cent of the patients had HbA1c < 7.0 per cent, 21.3 per cent had HbA1c 7.0-8.0 per cent and 29.3 per cent had HbA1c > 8.0 per cent. Adverse events that were probably or possibly related to the drug were reported in 5 patients (5.6%). Three of them were hypoglycemia and two patients had skin rash. All hypoglycemic episodes were mild. Glimepiride was indicated to be safe. There were no clinically significant changes in clinical laboratory values, physical examinations and vital signs. In conclusion, glimepiride was efficacious and safe in type 2 diabetes Thai patients and 1-2 mg of glimepiride appeared to be a sufficient dose for most newly diagnosed type 2 diabetic patients.

Glimepiride - A short term trial of the clinical efficacy

Diabetes is a common disorder and is reaching epidemic proportions especially in the third world. In the last few years new drugs have emerged targeting at better pharmacokinetic and low side effect profile. Among them have been various insulin sensitizers and newer sulfonylurias. Glimepiride with an impressive tract record offered more benefits and improved quality of life. The clinical efficacy in relation to the commonly used or traditional sulfonylurias was thus evaluated in this short term open trial involving 48 patients. The objective was to determine the clinical efficacy, tolerability, side effect profile and the equivalent dose of glimepiride compared to conventional sulphonylurias. The advantages of this new second generation sulfonyluria are discussed

Hipoglucemiante oral (HO) más acarbosa vs. hipoglucemiante oral más Psyllium plantago en el control metabólico del paciente diabético no insulinodependiente / Hypoglucemic agents plus acarbose vs hypoglycemic agents plus Psyllium plantago in the metabolic control of non-insulin-dependent diabetes mellitus

Antecedentes. La diabetes mellitus (DM) continúa siendo una causa muy importante de morbilidad y mortalidad. El propósito del tratamiento antidiabético es alcanzar la normoglucemia y de esta forma evitar las complicaciones tardías. Se han establecido diferentes estrategias terapéuticas, las cuales incluyen a la dieta, al ejercicio físico y los medicamentos, como sulfonilureas, biguanidas, insulina, inhibidores de las Ó-glucosidasas. Objetivo. Comparar la eficacia de la acarbosa o Psyllium plantago más hipoglucemiante oral en el control de la glucemia en el paciente diabético no insulinodependiente. Material y métodos. Estudio clínico abierto, con distribución al azar, controlado, con grupo paralelo. Los criterios de inclusión fueron: a) pacientes con diabetes mellitus no insulinodependiente con una concentración de hemoglobina glucosidada > 8 por ciento, pese a uso de hipoglucemiante oral y dieta; b) glucemia en ayuno > 140 mg/dl o glucemia posprandial de 2 horas > 180 mg/dl; c) depuración de creatinina > ml/min; d) niveles de LDL > 150 mg/dl. Se distribuyó al azar en los grupos de tratamiento de acuerdo con una tabla preestablecida, grupo de hipoglucemiante oral más acarbosa (A) y grupo de hipoglucemiante oral más Psyllium plantago(P). Se determinó glucemia en ayuno, glucemia posprandial de 2 horas, hemoglobina glucosilada, lipoproteínas de baja densidad (LDL). Se calculó frecuencia y medidas de tendencia central y dispersión de todas las variables y las variables cuantitativas se analizaron mediante la prueba de t de Student. La significancia estadística se estableció con un valor de p<0.05. Resultados. La hemoglobina glucosilada fue menor en el grupo A, con un promedio de 7.14 ñ 0.33 por ciento, mientras en el grupo P tuvo un valor de 9.62 ñ 0.48 por ciento (p<0.05); lo mismo ocurrió para los valores de glucemia en ayunas y posprandial de 2 horas; sin embargo, no se observó diferencia signficativa en las concentraciones de LDL. Conclusiones. Los resultados de nuestro estudio demuestran la utilidad de la acarbosa en combinación con hipoglucemiantes orales para disminuir la hemoglobina glucosilada y la hiperglucemia del paciente diabético crónicamente descontrolado

Sulfonilureas: estado actual de los conocimientos sobre su mecanismo de acción y su uso clínico / Sulfonylureas: present state of the knowledge on its mechanism of action and its clinic use

Las llamadas sulfonilureas de segunda generación comenzaron a emplearse extensamente en terapéutica durante la década de los setenta e incluyendo la glibenclamida, la gliclazida y la glipizida que se ha agregado recientemente la glimepirida. De una manera general, se encuentra que estas drogas actúan directamente sobre los islotes pancreáticos, aumentando la secreción de insulina por interacción entre la sulfoniluria y un receptor específico localizado en la membrana de las células beta. Se han descrito además efectos extrapancreáticos que consisten fundamentalmente en una potenciación de la acción metabólica que la insulina produce sobre los distintos tejidos efectores (hígado, tejido adiposo y muscular) y sobre la regulación de la producción hepática de glucosa. Las investigaciones acerca del mecanismo de estos efectos extrapancreáticos sugieren que ellos se deben a la estimulación de vías metabólicas situadas a nivel post-receptor. Teniendo en cuenta la fisiología de la diabetes no insulino-dependiente, la administración de sulfonilureas sigue siendo el método farmacológico dominante en el manejo de estos pacientes porque practicamente todos ellos son relativamente insulino-deficientes cuando la enfermedad se hace clínicamente manifiesta, y estas drogas mejoran tanto la secreción de insulina como su acción periférica

Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of non-insulin-dependent diabetes mellitus.

The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs. Acarbose, 100 mg three times daily, was additionally given to these patients for six months. Results showed small but significant decreases (P < 0.001) in postprandial blood glucose level. Glycosylated hemoglobin level was lowered significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of the patients. Fasting serum triglycerides level decreased significantly (P < 0.01), whereas, no significant changes in serum total cholesterol and HDL cholesterol levels were seen. Body weight also decreased significantly (P < 0.001) at the end of acarbose trial. Flatulence was the major side effect of acarbose found in 42 per cent of the patients but it was well-tolerated and may be transient and self-limited. We concluded that the addition of acarbose to the therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea combined with metformin drugs led to significant improvement of glycemic control. Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and metformin treatments in obese, poorly-controlled patients with NIDDM.

Combinación de insulina con sulfonilureas en pacientes diabéticos tipo II con control deficiente: estudio abierto / Combination therapy of insulin and sulfonylureas in type II diabetic patients with deficient control. An open study

El tratamiento combinado con insulina y sulfonilureas en pacientes diabéticos tipo II que no responden al tratamiento oral con hipoglucemiantes ha sido un tema de interés reciente. Varios estudios han demostrado mejoría en el control metabólico de la glucemia; sin embargo, no se han determinado las características que presentan los pacientes en los que se obtiene un mayor beneficio. En este estudio, durante 12 semanas evaluamos los resultados alcanzados con el tratamiento combinado de hipoglucemiantes orales por la mañana y de insulina a bajas dosis antes de la cena, en 35 pacientes diabéticos tipo II con falla secundaria a las sulfonilureas. Se demostró una mejoría significativa en el grupo estudiado, tanto en la glucemia de ayuno (de 14.9 a 7.81 mmol/l) como en la postprandial (de 14.09 a 10.86 mmol/l). Fue más notorio el beneficio en aquellos que al inicio del estudio presentaron cifras más altas de glucemia y de péptido C, así como en quienes tuvieron una mejor función renal valorada por medio del filtrado glomerular. La edad, el peso y el tiempo de evolución de la diabetes, no mostraron correlación. Se concluye que la terapia combinada es una buena elección, más aún si tomamos en cuenta los marcadores que correlacionan con un mayor beneficio

Farmacologia das sulfoniluréias / Pharmacology of sulfonylureas

No presente estudo foi descrita e evidenciada a farmacologia das sulfoniluréias, no tratamento do diabetes mellitus do tipo II (insulino-independente). Apesar da sempre crescente utilizaçäo destas drogas na terapia do diabetes, principalmente pela sua praticidade e rapidez, näo se pode deixar de esquecer o balanço entre as dosagens, contra-indicaçöes e o aspecto geral, físico e mental do paciente. Além disso, so cuidados gerais, a orientaçä para uma dieta equilibrada, a prática de exercício e os cuidados com a higiene pessoal do indivíduo diabético sä necessários para que o tratamento alcance o sucesso esperado

Effect of bed time intermediate acting insulin in NIDDM subjects refractory to a combination of sulphonylureas and biguanides.

The effect of a single dose of intermediate acting (Lente) insulin given subcutaneously at 9.00 P.M. in 22 NIDDM subjects refractory to a combination of Sulphonylureas and Biguanides was analysed. Euglycemia was achieved and maintained during the study period of three months with a mean insulin requirement of 14.22 +/- 5.98 units/day. Plasma FFA, Total cholesterol, triglyceride and VLDL-cholesterol also showed significant reduction. The level of FFA modulates hepatic glucose production, which in turn correlates positively with the fasting blood glucose. The therapeutic modality of bed time Lente Insulin based on physiological principles is an effective way of achieving glycemic control in NIDDM subjects who have become non-responsive to oral hypoglycemic agents.

Combination therapy of glibenclamide and insulin in NIDDM patients with secondary failure to oral drugs.

A trial of combination therapy with glibenclamide + insulin was conducted in 26 patients with non insulin dependent diabetes mellitus (NIDDM) who had secondary failure to oral hypoglycaemic agents (OHA). Patients were included in the study if they failed to respond to a dose of 15 mg of glibenclamide under strict dietary regulations. Small doses of insulin were added until satisfactory glucoregulation was achieved. On withdrawal of the OHA, in 20 patients, the post-prandial plasma glucose values (PPBS) increased again by greater than or equal to 25%; they were considered as "responders". Responders were divided into two equal groups of alternate patients; group I was treated with insulin + glibenclamide and group II with insulin + placebo. The patients were then followed up at monthly intervals for 6 months. The dose of insulin required to maintain normal plasma glucose value was significantly lower (P less than 0.05) in group I. Fewer patients in group I needed two injections of insulin per day; however this difference was not statistically significant. Normalisation of serum triglyceride and lowering of HbA1 occurred in both groups. This study shows that addition of glibenclamide to insulin treatment is advantageous in NIDDM patients showing secondary failure to OHA.