Comparison of Acarbose and Voglibose in Diabetes Patients Who Are Inadequately Controlled with Basal Insulin Treatment: Randomized, Parallel, Open-Label, Active-Controlled Study

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% +/- 0.71% to 7.71% +/- 0.93%) and voglibose groups (from 8.38% +/- 0.73% to 7.68% +/- 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 +/- 69.38 to 176.80 +/- 46.63 mg/dL) compared with the voglibose group (from 224.18 +/- 70.07 to 193.01 +/- 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528)

Actividad antioxidante y antihiperglucemiante de la especie medicinal Oreocallis grandiflora (Lam.) R. Br., al sur del Ecuador / Antioxidant and antihyperglycemic activity of the medicinal specie Oreocallis grandiflora (Lam.) R. Br., in southern Ecuador

In this study we evaluated the antioxidant and antihyperglycemic activity in vitro of the extracts obtained with solvents: hexane, ethyl acetate and methanol, of the medicinal plant Oreocallis grandiflora (cucharillo), collected in the Saraguro indian community of the province Loja, southern Ecuador. The antioxidant activity was evaluated by the tests: DPPH, FOLIN-CIOCALTEU and beta-CLAMS, while the antihyperglycemic activity was determined by inhibition assay á-amylase and alpha-glucosidase. The samples were diluted to different concentrations and the reading was performed in a UV spectrophotometer, using as positive control á-tocopherol for DPPH and Folin-ciocalteu test, trolox for beta-CLAMS test, and Glucobay® for testing alpha-amylase and alpha-glucosidase.The results are expressed as IC50, these show that the methanol extract of Oreocallis grandiflora has inhibitory effect on alpha-amylase, the IC50 is 109 ug/ml, compared to 126 ug/ ml of Glucobay®. It also shows inhibitory effect on á-glucosidase, the IC50 is 3 ug/ml compared to 1316 ug/ml of Glucobay®. It also shows antioxidant activity, its IC50 is 15 ug/ml compared to 5 ug/ml of á-tocopherol.

En el presente trabajo se evaluó la actividad antioxidante y antihiperglucemiante in vitro de los extractos obtenidos con los solventes: hexano, acetato de etilo y metanol, de la planta medicinal Oreocallis grandiflora (cucharillo), recolectada en la comunidad indígena de Saraguro en la provincia de Loja, al sur del Ecuador. La actividad antioxidante fue evaluada a través de los ensayos: DPPH, FOLIN-CIOCALTEU y beta-CLAMS, mientras que la actividad antihiperglucemiante fue determinada por el ensayo de inhibición de alfa- amilasa y alfa-glucosidasa. El extracto metanólico de Oreocallis grandiflora presenta efecto inhibitorio sobre la enzima alfa-amilasa, su concentración inhibitoria (CI50) es de 109 ug/ml, frente a 126 ug/ml del control positivo Glucobay®. Además, muestra efecto inhibitorio sobre la enzima alfa-glucosidasa, su concentración inhibitoria (CI50) es de 3 ug/ml, frente a 1316 ug/ml del Glucobay®. Muestra también actividad antioxidante, su concentración inhibitoria (CI50) es de 15 ug/ml, frente a 5 ug/ml del alfa-tocoferol.

Diabetes Mellitus Tipo 2 no mundo: atualização do tratamento medicamentoso / Type 2 Diabetes Mellitus in the world: an update of drug treatment

O diabetes mellitus tipo 2 (DM2) está alcançando proporções epidêmicas, e embora as mudanças no estilo de vida possam manter o controle glicêmico, o curso da doença, em longo prazo, requer algum tipo de intervenção farmacológica. É bem conhecido que os indivíduos que se mantêm mal controlados apresentam mais complicações macro e microvasculares e a redução da hemoglobina glicada (HbA1c) diminui significativamente o risco de desenvolvimento de complicações microvasculares em pacientes com DM2. Atualmente há seis classes de antidiabéticos orais: sulfonilureias, meglitinidas, biguanidas, tiazolidinedionas (TZDs), inibidores da alfa-glicosidase e os incretinomiméticos. As sulfonilureias e as meglitinidas estimulam a secreção de insulina; a metformina age principalmente suprimindo a produção hepática de glicose; as tiazolidinedionas melhoram a resistência periférica à insulina e os inibidores da alfa-glicosidase retardam a degredação e a digestão dos carboidratos complexos no intestino. Uma nova opção terapêutica para o DM2 são as drogas incretinomiméticas. Dentre elas temos os análogos de GLP-1 (exenatida e liraglutida) e os inibidores da DPP-IV. Ambos estimulam a secreção de insulina, suprimem a secreção de glucagon e desaceleram o esvaziamento gástrico; a redução de peso é característica dos análogos. O bom controle glicêmico em longo prazo e a prevenção do DM2 requerem uma abordagem agressiva e abrangente. No entanto, uma vez instalada a doença, além das modificações do estilo de vida, o tratamento farmacológico deve ser iniciado e cuidadosamente monitorado, com o uso de drogas que agem nos diversos mecanismos fisiopatológicos conhecidos. Novos estudos serão sempre necessários para se obter mais informações a respeito do diabetes e, assim, aprimorar o desenvolvimento de novas drogas.

The type 2 diabetes has reached epidemic proportions in the worldwide and lifestyle modification provide insufficient glucose control over the long-term course of the disease, the vast majority of patients require some type of pharmacological intervention. Several studies have shown that individuals who remain poorly controlled have more macro and microvascular complications and the decrease in glycated hemoglobin (HbA1c) significantly reduces the risk of developing microvascular complications in type 2 diabetes. At the moment, there are six classes of oral antidiabetics drugs: sulfonylureas, meglitinides, biguanides (metformin), thiazolidinediones (pioglitazone), alpha-glucosidase inhibitors (acarbose) and incretin-mimetics drugs. The sulfonylureas and meglitinide acting insulin secretion; metformin acts primarily by suppressing hepatic glucose production; thiazolidinediones improve insulin resistance; and alpha-glucosidade inhibitors retard the degradation and digestion of complex carbohydrates in the intestine and incretin-mimetics drugs that stimulate insulin secretion, suppress glucagon secretion, slows gastric emptying and weight loss (it is characteristic of the GLP-1 analogues). The good longterm glycemic control and prevention of type 2 diabetes requires an aggressive and comprehensive approach. However, once installed the disease, in addition to lifestyle modifications, pharmacotherapy should be initiated and carefully monitored using drugs that act on different pathophysiologicals mechanisms. New studies are always necessary to obtain more information about diabetes and thus improve the development of new drugs.

Recent advances in pharmacotherapy for type-2 diabetes: a review [part 1]

The global incidence of Type-2 diabetes is on the rise and the public health and resource implications of the disease will be very enormous. The therapeutic armamentarium has been very much static up to the last decade of the last century when more several agents were developed and marketed. New oral agents followed the footsteps of the sulphonylureas and biguanides, and agents like the alpha-glucosidase inhibitors, meglitinides, thiazolidinediones and incretin-based therapeutic agents have added a new dimension to the management of the disease and more options for the increasing number of patients. Other novel agents are still in development. Furthermore, advances in scientific research and clinical practice and patient's care have shed the light on the importance of the holistic approach for management of these patients, and the need to address the devastating complications and the best way of achieving this. This paper is the first part of a series of reviews that is aimed at surfing the current developments in pharmacotherapy of Type-2 diabetes

Nuevos fármacos en diabetes tipo 2 / New drugs in diabetes mellitus type 2

La diabetes tipo 2 asociada a obesidad en un 80% es actualmente la enfermedad metabólica de mayor prevalencia y de mayor morbimortalidad causada en un 60% por enfermedad cardiovascular. La podemos controlar en parte, pero no curar. El mayor problema patológico social y económico lo constituyen las complicaciones, si bien las microvasculares responden en parte al control de la glicemia, no lo hacen del mismo modo las cardiovasculares. El tratamiento no está exento de riesgo, la hipoglicemia y el aumento de peso cuando se trata de cumplir metas exigentes, con algunos fármacos disponibles, son los efectos adversos que se observan con mayor frecuencia. Ambos limitan las metas del tratamiento, atemorizando al paciente y provocando inercia médica Por 50 años los fármacos experimentaron pocas modificaciones, insulina, sulfonilureas y biguanidas estuvieron orientados a bajar la glicemia, sin embargo hoy hemos aprendido que la hiperglicemia es la consecuencia de un islote pancreático enfermo y que los fármacos deben apuntar en sentido más amplio, preservado células beta y la función corrigiendo además el problema periférico que constituye la insulinorresistencia, sin aumentar el daño vascular de la diabetes. La visión más amplia ha cambiado el paradigma patogénico y terapéutico, motivando la búsqueda de nuevos fármacos que han motivado esta revisión.

Diabetes mellitus type 2 associated with obesity in a 80% is actually the metabolic disease of major prevalence, and major morbimortality, causing in a 60% cardiovascular disease. These can be partly controlled, but not cure. The great social pathologic and economic problem, are the complications, the microvascular respond to the glycemia control, but with the cardiovascular complications doesn 't respond in the same way. The treatment with some available pharmacos is not free of risk; there are some adverse effects that can be observe with major frequency, like hypoglycemia and weigh in crease. 80th of them restrain the treatment goals, frightening the patient and produce medical inertia. For fifty years pharmacos used in diabetes treatment had experimented few modifications, insulin, sulfonylurea and biguanidins were orientated to reduce glycemia, however today we have learn that hyperglycemia is the consequence of a sick pancreatic islet, and that the medication must be orientated in a more wider sense, preserving beta cells, and its function, modifying also the periphery problem, the insulin resistance component, without increasing the diabetes vascular damage. An amplifying vision had changed the pathogenic and therapeutic paradigm, motivating the search of new pharmacos, goal that motive this revision.

Agentes farmacológicos actuales en el tratamiento de la Diabetes Mellitus no Insulinodependiente / Present pharmacological agents in the treatment of non-insulin-dependent diabetes

Se plantea que debido a la heterogeneidad patogénica de la diabetes mellitus no insulino, se debe considerar que diferentes agentes farmacológicos serán necesarios para tratar con éxito la enfermedad, por lo cual se realiza una revisión bibliográfica de las líneas de tratamiento actuales y en perspectivas para esta compleja entidad. Las modalidades terpéuticas actuales incluyen 5 grupos de agentes esenciales: los inhibidores de las alfaglucosidasas intestinales, las sulfonilureas, las biguanidas, la insulina y el recién incorporado grupo de las tiazolidinedionas, que si se utilizan en los comienzos de la enfermedad o en pacientes con resistencia insulínica, pudieran retrasar o prevenir el desarrollo de ésta, y pueden interferir en la reducción progresiva de la función pancreática. Se expone un grupo importante de agentes farmacológicos, así como sus posibles mecanismos de acción, sobre los cuales se ha estado investigando, para ampliar e incrementar la terapéutica de la diabetes, entre los que se encuentran los análogos de la insulina, los agentes insulinomiméticos y los preparados orales de insulina, los agentes insulinotrópicos no sulfonilureas, los análogos de la amilina, los péptidos similares al glucagón, los antagonistas alfa-2 adrenérgicos, los moduladores del metabolismo de la glucosa y algunas sustancias de origen vegetal con posibles efectos hipoglucémicos

Plants as hypoglycemic agents

The world over, many plants are being used successfully - mainly in the form of teas - to counteract the effects of diabetes; and Brazil is no exception. This is especially true for patients suffering from noninsulin dependent (type II) diabetes. The article first summarizes the mechanisms reported in the scientific literature which explain hypoglycemic activity in plants. These include: Inhibition of the intestinal absorption of glucose; inhibition of alpha-glucosidase; and protection of the beta-pancreatic cells and of the liberated insulin. Also shown is the hypoglycemic activity of glycans. In a second section experimental results are presented with three plants widely used in Brazil as hypoglycemic agents: Myrcia multiflora (Lam.) D.C. (pedra-ume-caá); Punica granatum L. (roma, pomegranate); and Chrysobalanus icaco (abajeru). The experimental results show the activity of the plant extracts in the inhibition of the intestinal absorption of glucose.

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.

Eficacia y tolerancia de acarbose en pacientes diabéticos no dependientes de insulina / Efficacy and tolerance of acarbose in non-insulin dependent diabetes

El acarbose es un inhibidor competitivo de aglucosidasa que reduce el aumento postprandial de glucosa e insulina. En este estudio doble ciego, cruzado, con distribución de tratamientos al azar, se administró acarbose o placebo a un grupo de pacientes con DMNID crónicamente descontrolados que recibían sulfonilureas. Los pacientes continuaron su tratamiento previo y fueron distribuidos al azar en dos secuencias: en la A recibieron acarbose 100 mg tres veces al día 12 semanas, dos semanas de placebo tres veces al día (periodo de lavado) y finalmente placebo tres veces al día 12 semanas. En la secuencia B el orden fue inverso al anterior (placebo-placebo-acarbose). Se incluyeron 16 pacientes en cada secuencia. Se excluyeron tres de la secuencia A: uno por efectos colaterales, uno por dolor neuropático y uno por cambio de domicilio. De la secuencia B se excluyó uno por no tomar la sulfonilurea. Se observó una disminución discreta pero significativa del peso con acarbose comparado con placebo en ambas secuencias. Se observaron reducciones significativas de glucosa postprandial con el acarbose en ambas secuencias; también se observaron reducciones en los niveles de glucosa de ayunas en algunas visitas. Aunque los valores promedio de HbA1c y triglicéridos fueron menores con acarbose, la diferencia con el placebo no fue estadísticamente significativa. El acarbose fue tolerado bien en general, ya que si bien casi todos los pacientes mostraron efectos colaterales, sólo tuvo que suspenderse en uno. El acarbose es un recurso terapéutico útil en combinación con sulfonilureas en diabéticos no insulinodependiente