RESUMEN
Liraglutide, an analog of the incretin hormone glucagon-like peptide 1 (GLP-1), is widely used for obesity and type 2 diabetes treatment. However, there is scarce information about its effects on testicular function. Within the testis, Sertoli cells (SCs) provide nutritional support for germ cells; they metabolize glucose to lactate, which is delivered to germ cells to be used as a preferred energy substrate. Besides, SCs use fatty acids (FAs) as an energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as an important energy reserve. In the present study, 20-day-old rat SC cultures were used to assess whether liraglutide affects their metabolic functions related to nutritional support and lipid storage. The results show that liraglutide does not modify glucose consumption or lactate production. However, it increases TAG levels and LD content. These effects are accompanied by an increase in the mRNA levels of the fatty acid transporter FAT/CD36, glycerol-3-phosphate-acyltransferase 3, and perilipins 1 and 4. The participation of the cAMP/PKA signaling pathway was explored. We observed that H89 (a PKA inhibitor) decreases the LD upregulation elicited by liraglutide, and that dibutyryl cAMP increases LD content and the expression of related genes. In summary, liraglutide promotes lipid storage in SCs through the regulation of key regulatory genes involved in FA transport, TAG synthesis, and LD formation. Considering the importance of lipid storage in SC energetic homeostasis maintenance, we postulate that liraglutide might improve the overall energetic status of the seminiferous tubule.
Asunto(s)
Metabolismo Energético , Liraglutida , Células de Sertoli , Animales , Masculino , Liraglutida/farmacología , Células de Sertoli/metabolismo , Células de Sertoli/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Ratas , Células Cultivadas , Péptido 1 Similar al Glucagón/metabolismo , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/farmacología , Triglicéridos/metabolismo , Glucosa/metabolismo , Gotas Lipídicas/metabolismo , Gotas Lipídicas/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Antígenos CD36/metabolismo , Antígenos CD36/genéticaRESUMEN
CONTEXTO: El sobrepeso y la obesidad constituyen un importante problema de salud pública en todo el mundo. El tratamiento inicial consta de modificación del estilo de vida (LSM, por sus siglas en inglés) y en caso de falla, se inicia con tratamiento farmacológico como semaglutida, la cual está aprobada por agencias regulatorias internacionales y nacionales para el sobrepeso con un IMC de ≥ 25 kg/m2 a ≤ 29.9 kg/m2 y la obesidad con un IMC ≥ 30 kg/m2. El objetivo de este informe es revisar la eficacia clínica, la seguridad y la costo-efectividad de semaglutida en comparación con liraglutida para el tratamiento del sobrepeso y obesidad en la población en edad adulta sin Diabetes Mellitus tipo 2 (DM2). Ambos medicamentos cuentan con registro sanitario expedido por la Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) para el tratamiento del sobrepeso y obesidad en la población en edad adulta, así como para el tratamiento de la DM2; sin embargo, en el Compendio Nacional de Insumos para la Salud (CNIS), se encuentran disponibles solamente para el tratamiento de la población en edad adulta con DM2. MÉTODOS: Se realizó una búsqueda sistemática de la literatura en diversas bases de datos. Se seleccionaron 13 documentos relevantes (2 revisiones sistemáticas [RS] con metanálisis en red [NMA, por sus siglas en inglés], 5 ensayos clínicos aleatorios [ECAs], 3 evaluaciones económicas y 3 evaluaciones de tecnologías para la salud). Las medidas de resultado fueron el cambio del peso corporal, porcentaje de eventos adversos (EAs), costos y la razón costo-efectividad incremental (RCEI). RESULTADOS: En la RS con NMA de Smith et al. (2022)2 , los resultados mostraron que, en pacientes en edad adulta con sobrepeso y obesidad, sin DM2 y con LSM, la diferencia porcentual del cambio en el peso desde el estado basal con semaglutida versus liraglutida fue de -7.02 (intervalo de confianza [IC] del 95%: - 9.61 a -4.41, 23 de 32 puntos del PRISMA NMA con un riesgo de sesgo alto) y con respecto a placebo, la diferencia porcentual fue de -12.43 (IC del 95%: -14.51 a -10.38). Los resultados para la RS con NMA de Vosoughi et al. (2021)3 , en esta misma población, indica que la diferencia de medias (DM) del cambio en el peso desde el estado basal con semaglutida versus liraglutida fue de -5.53 (IC del 95%: -7.45 a - 3.60, en 4 estudios, 52 semanas de seguimiento, con 29 de 32 puntos del PRISMA NMA con un riesgo de sesgo alto) y en la escala SUCRA semaglutida obtuvo una clasificación del 100%, lo que indica que refleja una mayor probabilidad de ser más efectiva en términos de pérdida de peso y con una menor probabilidad de presentar EAs. CONCLUSIONES: Los 5 ECAs48 , concluyeron que semaglutida, a una dosis de mantenimiento de 2.4 mg, presentó mayor eficacia frente a liraglutida 3.0 mg (dosis de mantenimiento) y placebo, y con una seguridad similar a la esperada en el grupo de los análogos del péptido similar al glucagón tipo 1 (GLP-1). En dos evaluaciones económicas9,10 se indicó que semaglutida fue costo-efectiva versus sus respectivos comparadores. En Kim et al. (2022) 9 los comparadores utilizados fueron ningún tratamiento, dieta y ejercicio (D&E), liraglutida 3.0 mg, fentermina/topiramato y naltrexona/bupropión; mientras que en Olivieri et al. (2022) 10 los comparadores considerados fueron D&E sola, liraglutida 3.0 mg, orlistat y naltrexona 32 mg/bupropión. Sin embargo, un tercer estudio11 mostró que semaglutida no fue costo-efectiva dados los umbrales de disposición a pagar aceptados. Los hallazgos deben interpretarse con cautela considerando las limitaciones tanto clínicas como económicas. Se requieren más estudios de semaglutida que investiguen sobre los efectos a largo plazo, estudios directos versus otras opciones de tratamiento farmacológico, y el efecto en las comorbilidades y mortalidad, con el objetivo de comprender de una mejor manera la eficacia, seguridad y costo-efectividad de semaglutida en el tratamiento de pacientes en edad adulta con sobrepeso y obesidad. De acuerdo al análisis crítico la evidencia clínica fue predominantemente de baja certeza según GRADEpro, además de un riesgo de sesgo muy serio. Con respecto a los estudios de evaluación económica, la evidencia mostró que semaglutida 2.4 mg vía SC una vez a la semana como complemento a la LSM, fue más eficaz, segura y costo-efectiva en comparación con liraglutida 3.0 mg más LSM y LSM en la población de participantes con sobrepeso y obesidad sin DM2; de acuerdo a la disponibilidad a pagar que se describe en los estudios.
Asunto(s)
Humanos , Sobrepeso/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Evaluación en Salud/economía , Eficacia , Análisis Costo-Beneficio/economíaRESUMEN
Type 2 diabetes is a fast-growing worldwide epidemic. Despite the multiple therapies available to treat type 2 diabetes, the disease is not correctly managed in over half of patients, mainly due to non-compliance with prescribed treatment regimes. The development of analogues to the glucagon-like peptide 1 (GLP-1) has resulted in the extension of its half-life and associated benefits. Further benefits in the use of peptide-based GLP-1 receptor agonists have been achieved by the use of controlled-release systems based on polymeric microparticles. In this review, we focus on commercially available formulations and others that remain in development, discussing the preparation methods and the relationship between in vitro and in vivo kinetic release behaviours.
Asunto(s)
Péptido 1 Similar al Glucagón/análogos & derivados , Receptor del Péptido 1 Similar al Glucagón/agonistas , Polímeros/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Composición de Medicamentos , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Tamaño de la PartículaRESUMEN
The current absence of effective treatments for Alzheimer's disease (AD) and Parkinson's disease (PD) reflects an incomplete knowledge of the underlying disease processes. Considerable efforts have been made to investigate the central pathological features of these diseases, giving rise to numerous attempts to develop compounds that interfere with such features. However, further characterization of the molecular targets within the interconnected AD and PD pathways is still required. Impaired brain insulin signaling has emerged as a feature that contributes to neuronal dysfunction in both AD and PD, leading to strategies aiming at restoring this pathway in the brain. Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for treatment of type 2 diabetes mellitus have been tested and have shown encouraging protective actions in experimental models of AD and PD as well as in initial clinical trials. We review studies revealing the neuroprotective actions of GLP-1 analogues in pre-clinical models of AD and PD and promising results from recent clinical trials.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Péptido 1 Similar al Glucagón/análogos & derivados , Resistencia a la Insulina , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/metabolismo , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Enfermedad de Parkinson/metabolismoRESUMEN
The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates.
Asunto(s)
Hepatopatías/prevención & control , Trasplante de Hígado , Péptidos/administración & dosificación , Ponzoñas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Muerte Encefálica/metabolismo , Caspasa 3/biosíntesis , Caspasa 3/genética , Citocinas/biosíntesis , Citocinas/genética , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Exenatida , Regulación de la Expresión Génica , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Immunoblotting , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/genética , Hepatopatías/metabolismo , Masculino , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la PolimerasaAsunto(s)
Aprobación de Drogas , Quimioterapia/enfermería , Anticuerpos Monoclonales Humanizados/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Benzofuranos/uso terapéutico , Ciclopropanos/uso terapéutico , Difosfatos/uso terapéutico , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/uso terapéutico , Glucósidos/uso terapéutico , Glicopéptidos/uso terapéutico , Humanos , Lactonas/uso terapéutico , Lipoglucopéptidos , Organofosfatos/uso terapéutico , Oxazoles/uso terapéutico , Piridinas/uso terapéutico , Sulfatos/uso terapéutico , Teicoplanina/análogos & derivados , Teicoplanina/uso terapéutico , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Liraglutide is an agonist of the glucagon-like peptide I receptor, and is commonly recommended as a treatment for obesity and type 2 diabetes mellitus. Adverse effects related to liraglutide include acute pancreatitis and polyarthritis. No studies, however, have reported an adverse effect of liraglutide on male reproduction. This case report shows a deleterious effect of liraglutide on male reproductive function.
Asunto(s)
Fertilidad/efectos de los fármacos , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/efectos adversos , Infertilidad Masculina/inducido químicamente , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Péptido 1 Similar al Glucagón/efectos adversos , Humanos , Liraglutida , Masculino , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Embarazo , Resultado del Embarazo , Recuento de Espermatozoides , Inyecciones de Esperma Intracitoplasmáticas , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacosAsunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , /tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Biomarcadores/metabolismo , /metabolismo , Péptido 1 Similar al Glucagón/uso terapéutico , Medición de RiesgoRESUMEN
OBJECTIVE: To evaluate the results of the use of liraglutide in a group of patients undergoing surgical treatment of morbid obesity with unsatisfactory weight loss or regain of more than 15% of minimum reached weight. METHODS: The authors conducted a retrospective analysis of 15 operated patients who had excess weight loss <50% after two years of follow-up or regained weight more than 15% of the minimum reached weight. We included only patients who had the expected "surgical anatomy", assessed by contrast radiography and endoscopy. Mean age was 47.2 ± 12.5 years, and patients received liraglutide at doses from 1.2 to 3.0 mg/day for eight to 28 weeks follow-up. RESULTS: Surgical treatment induced a weight loss of 34.1 ± 16.5 kg. The average weight regain after 5.3 ± 3.3 years was 14.2 ± 12.1 Kg. The average weight was significantly reduced after treatment with liraglutide (100.9 ± 18.3 kg. vs Kg 93.5 ± 17.4, p <0.0001). Six patients had nausea and two discontinued therapy due to the cost of medication. CONCLUSION: medical treatment directed to the control of satiety using liraglutide may be an alternative treatment of patients with poor weight loss or weight regain after surgery when no technical problem has been identified.
Asunto(s)
Cirugía Bariátrica , Péptido 1 Similar al Glucagón/análogos & derivados , Obesidad Mórbida/cirugía , Aumento de Peso , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
OBJETIVO: avaliar os resultados da utilização do liraglutide em um grupo de pacientes submetidos ao tratamento cirúrgico da obesidade mórbida com perda insatisfatória de peso ou ganho de mais de 15% do seu peso mínimo atingido. MÉTODOS: realizou-se análise retrospectiva de 15 pacientes operados que tiveram perda de excesso de peso <50% após dois anos de seguimento ou reganho de peso de mais de 15% do peso mínimo atingido. Foram incluídos apenas pacientes que apresentavam a "anatomia cirúrgica" normal avaliada por radiografia contrastada e endoscopia digestiva alta. A média de idade foi 47,2±12,5 anos e os pacientes receberam liraglutide na dose de 1,2 a 3,0mg/dia por oito a 28 semanas de seguimento. RESULTADOS: o tratamento cirúrgico induziu uma perda de peso de 34,1± 16,5Kg. A média de reganho de peso após 5,3 ±3,3 anos foi 14,2±12,1Kg. A media de peso reduziu significativamente após o tratamento com liraglutide (100,9±18,3Kg vs. 93,5±17,4Kg; p<0,0001). Seis pacientes apresentaram náuseas e dois descontinuaram o tratamento em decorrência do custo da medicação. CONCLUSÃO: o tratamento clínico medicamentoso dirigido para o controle da saciedade com o uso do liraglutide pode ser uma alternativa para manejo dos pacientes com reganho de peso ou perda insuficiente após o tratamento cirúrgico, quando nenhum problema técnico tenha sido identificado.
OBJECTIVE: To evaluate the results of the use of liraglutide in a group of patients undergoing surgical treatment of morbid obesity with unsatisfactory weight loss or regain of more than 15% of minimum reached weight. METHODS: The authors conducted a retrospective analysis of 15 operated patients who had excess weight loss <50% after two years of follow-up or regained weight more than 15% of the minimum reached weight. We included only patients who had the expected "surgical anatomy", assessed by contrast radiography and endoscopy. Mean age was 47.2 ± 12.5 years, and patients received liraglutide at doses from 1.2 to 3.0 mg/day for eight to 28 weeks follow-up. RESULTS: Surgical treatment induced a weight loss of 34.1 ± 16.5 kg. The average weight regain after 5.3 ± 3.3 years was 14.2 ± 12.1 Kg. The average weight was significantly reduced after treatment with liraglutide (100.9 ± 18.3 kg. vs Kg 93.5 ± 17.4, p <0.0001). Six patients had nausea and two discontinued therapy due to the cost of medication. CONCLUSION: medical treatment directed to the control of satiety using liraglutide may be an alternative treatment of patients with poor weight loss or weight regain after surgery when no technical problem has been identified.
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirugía Bariátrica , Péptido 1 Similar al Glucagón/análogos & derivados , Obesidad Mórbida/cirugía , Aumento de Peso , Péptido 1 Similar al Glucagón/administración & dosificación , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del TratamientoAsunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Medición de Riesgo , Adulto JovenRESUMEN
New drugs for type 2 diabetes that act on incretin metabolism have been shown to improve glycemic control, reduce body weight and have a low risk for hypoglycemia. Among these, liraglutide is the first glucagon-like peptide 1 (GLP-1) analogue approved for subcutaneous, once-daily administration. According to results from clinical trials, liraglutide is an attractive alternative for the early treatment of type 2 diabetes. The results of the LEAD (Liraglutide Effect and Action in Diabetes) study program demonstrated the efficacy and safety of liraglutide in terms of reduction of glycated hemoglobin (HbA1c) levels, significant loss of body weight that was maintained over the long term, better control of the lipid profile and systolic arterial pressure, reduction of the risk for hypoglycemia and reduction of cardiovascular risk. Moreover, the drug was demonstrated to be safe and can be co-administered with oral antidiabetic agents. The product's tolerability has been demonstrated, with nausea as the most common adverse event, which waned from the fourth week of treatment.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Péptido 1 Similar al Glucagón/efectos adversos , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Incretinas/metabolismo , Liraglutida , Pirazinas/uso terapéutico , Fosfato de Sitagliptina , Compuestos de Sulfonilurea/uso terapéutico , Triazoles/uso terapéuticoRESUMEN
In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP 4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.
Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Células Secretoras de Insulina/citología , Animales , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Glucosa/metabolismo , Homeostasis , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Liraglutida , Modelos Biológicos , PPAR gamma/metabolismo , Tiazolidinedionas/farmacologíaRESUMEN
In the gastrointestinal tract we produce hormones, called incretins, in response to food ingestion with a direct effect on pancreatic ß and α cell improving the insulin and glucagon response to glucose. The effect consisting in a greater secretion of insulin with a glucose stimulus from the gut or IV injection is called "the incretin effect." The main incretins are: glucagon like peptide-1 (GLP1) and glucose-dependent insulinotropic peptide (GIP). The action of both incretins is very short due to a rapid inhibition in the circulation by an enzyme dipeptylpeptidase IV (DPP4). In type 2 diabetics, the incretin effect is altered and can be improved by elaboration of a GLP1 resistant to the action of DPP4 (GLP1 analogs) or by direct inhibition of DPP4 producing better effect of native GLP1 and GIP. We have exenatide a derivative from exendin 4, and liraglutide very similar to the native human GLP1. Three inhibitors of DPP4: sitagliptin, and vildagliptin and saxagliptin produce a prolonged inhibition of DPP4 and as a consequence increased effect of native incretins with better control of fasting and postprandial glucose and improve on A1c with a very few hypoglycemic events.
Asunto(s)
Diabetes Mellitus Tipo 2/etiología , Incretinas/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Péptido 1 Similar al Glucagón/análogos & derivados , Humanos , Células Secretoras de Insulina/fisiologíaRESUMEN
OBJECTIVE: To compare the efficacy of liraglutide monotherapy with glimepiride monotherapy in subjects with DM2 inadequately controlled by previous treatment of diet/exercise or oral antidiabetic drug. METHODS: A 52-week, double-blinded, active-controlled, parallel-group, multi-centre, prospective trial, involving 746 subjects was conducted in the USA and Mexico. In Mexico, 171 subjects were rando-mised (1:1:1) to once daily liraglutide (either 1.2, or 1.8 mg/day injected subcutaneously) or glimepiride (8 mg/day orally). RESULTS: Hb1Ac reduced by 0.64%, 1.31% and 0.30% with glimepiride, liraglutide 1.8 mg and 1.2 mg, respectively. Body weight decreased with both liraglutide doses while a weight gain of 0.94 kg was observed with glimepiride. FPG reduced by 27.9 mg/dL with liraglutide 1.8 mg, whereas a FPG increase of 9.54 mg/dL was shown with glimepiride. No major hypoglycaemic episodes were reported in this trial. CONCLUSIONS: in Mexican subjects with DM2, liraglutide monotherapy can provide greater reduction in HbA1c, weight loss and lower risk of hypoglycaemia in comparison with glimepiride.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Liraglutida , Masculino , México , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1), whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes , Insulina , Administración por Inhalación , Administración Oral , Amiloide/agonistas , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Péptido 1 Similar al Glucagón/análogos & derivados , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Inyecciones Subcutáneas , Insulina/administración & dosificación , Polipéptido Amiloide de los Islotes PancreáticosRESUMEN
Novos medicamentos para o tratamento do diabetes tipo 1 e tipo 2 foram incorporados à lista de fármacos tradicionais: antidiabéticos orais e insulinas injetáveis. Estas alternativas de tratamento têm novos mecanismos de ação que aproveitam as propriedades antidiabéticas de certos peptídeos como é o caso da amilina ou do peptídeo similar ao glucagon (GLP-1), cujos níveis são deficientes ou insuficientes no diabetes. Isto acontece pelos análogos da amilina ou do GLP-1, embora também possa ser obtido inibindo a enzima que degrada este último. Além disso, encontra-se disponível no mercado um novo sistema para administrar insulina de maneira não-invasiva por meio de inalação. Este artigo resume os resultados mais importantes e atualizados com relação ao mecanismo de ação, eficácia, efeitos adversos e indicações destes fármacos inovadores.
New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1), whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.
Asunto(s)
Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , /tratamiento farmacológico , Hipoglucemiantes , Insulina , Administración por Inhalación , Administración Oral , Amiloide/agonistas , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Inyecciones Subcutáneas , Insulina/administración & dosificaciónRESUMEN
The prevalence of diabetes and impaired glucose tolerance is predicted to dramatically increase over the next two decades. Clinical therapies for type 2 diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral anti-diabetic agents, and ultimately insulin initiation. In this report, we review the clinical trial results of two innovative T2DM treatment therapies that are based on the glucoregulatory effects of incretin hormones. Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. Additionally, incretin mimetics lower postprandial and fasting glucose, suppress elevated glucagon release, and are associated with progressive weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies in patients with T2DM have shown that DPP-4 inhibitors reduce elevated A1C, lower postprandial and fasting glucose, suppress glucagon release, and are weight neutral. Collectively, these new drugs, given in combination with other antidiabetic agents, such as metformin, sulfonylureas, and/or thiazolidinediones, can help restore glucose homeostasis in poorly controlled patients with T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Incretinas/uso terapéutico , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Exenatida , Ayuno , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/efectos de los fármacos , Hemoglobina Glucada/efectos de los fármacos , Humanos , Nitrilos/uso terapéutico , Péptidos/uso terapéutico , Periodo Posprandial , Pirazinas/uso terapéutico , Pirrolidinas/uso terapéutico , Fosfato de Sitagliptina , Triazoles/uso terapéutico , Ponzoñas/uso terapéutico , VildagliptinaRESUMEN
The prevalence of diabetes and impaired glucose tolerance is predicted to dramatically increase over the next two decades. Clinical therapies for type 2 diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral anti-diabetic agents, and ultimately insulin initiation. In this report, we review the clinical trial results of two innovative T2DM treatment therapies that are based on the glucoregulatory effects of incretin hormones. Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. Additionally, incretin mimetics lower postprandial and fasting glucose, suppress elevated glucagon release, and are associated with progressive weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies in patients with T2DM have shown that DPP-4 inhibitors reduce elevated A1C, lower postprandial and fasting glucose, suppress glucagon release, and are weight neutral. Collectively, these new drugs, given in combination with other antidiabetic agents, such as metformin, sulfonylureas, and/or thiazolidinediones, can help restore glucose homeostasis in poorly controlled patients with T2DM.
É previsto que a prevalência de diabetes e a intolerância à glicose aumente dramaticamente ao longo das próximas duas décadas. As terapias clínicas para diabetes melito tipo 2 (DM2) têm tradicionalmente incluído modificação do estilo de vida, agentes antidiabéticos orais e, por último, o início da insulina. Neste artigo, revisamos os resultados dos estudos clínicos de duas terapias inovadoras no tratamento do DM2 baseadas nos efeitos glicorregulatórios dos hormônios incretina. Os incretinomiméticos são medicamentos peptídeos que mimetizam várias das ações do peptídeo semelhante ao glucagon-1 (GLP-1) e têm demonstrado reduzir níveis de hemoglobina glicada (A1C) em pacientes com DM2. Adicionalmente, incretinomiméticos reduzem as glicemias pós-prandial e de jejum, suprimem a liberação elevada do glucagon, e são associados com redução de peso. Os inibidores da dipeptidil peptidase-4 (DPP-4) aumentam os níveis de GLP-1 endógeno pela inibição da degradação enzimática do GLP-1. Estudos clínicos em pacientes com DM2 têm demonstrado que inibidores da DPP-4 reduzem A1C elevada, reduzem as glicemias pós-prandial e de jejum, suprimem a liberação elevada do glucagon e são neutros quanto ao peso. Coletivamente, estas novas medicações, administradas em combinação com outros agentes antidiabéticos, como metformina, sulfoniluréias e/ou tiazolidinedionas (TZDs), podem ajudar a recuperar a homeostase glicêmica de pacientes com DM2 não-controlados.