ABSTRACT
En este artículo, la autora jerarquiza la relevancia de la eficacia documentada de los agonistas del péptido similar alglucagón-1 y los inhibidores del cotransportador sodio-glucosa tipo 2, que ha conducido a recientes modificaciones en el paradigma del cuidado en los pacientes con diabetes tipo 2. (AU)
In this article, the author highlights the relevance of the documented efficacy of glucagon-like peptide-1 agonists and type 2 sodium-glucose cotransporter inhibitors, which has led to recent changes in the paradigm of care in patients with type 2diabetes. (AU)
Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1/therapeutic use , Glucagon-Like Peptide 1/agonists , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic useSubject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1/agonists , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Incretins/adverse effects , Review Literature as Topic , Randomized Controlled Trials as Topic , Meta-Analysis as Topic , Diabetes Mellitus, Type 2/mortality , Diabetic Angiopathies/chemically induced , Diabetic Angiopathies/mortality , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Incretins/therapeutic use , Systematic Reviews as Topic , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic useABSTRACT
O diabetes mellitus tipo 2 (DM2) apresenta alta prevalência, com aumento inclusive em crianças e adolescentes. A importância de um estrito controle glicêmico pode ser comprovada com a redução das complicações crônicas microvasculares. Já em relação à redução da doença macrovascular, principal causa de mortalidade nestes pacientes, são fundamentais o controle da glicemia, bem como de outros fatores de risco cardiovasculares, tais como hipertensão arterial, dislipidemia, peso, e a manutenção de hábitos saudáveis de vida. Temos vários medicamentos para o tratamento do DM2, sendo que a metformina é ainda a droga de primeira escolha, devido ao seu baixo custo e eficácia comprovada...
Type 2 diabetes mellitus (DM2) is highly prevalent and is increasing even in children and adolescents. The importance of strict glycemic control can be proven to reduce chronic microvascular complications. Regarding the reduction of macrovascular disease, the leading cause of mortality in these patients, it is essential tight glycemic control, as well as other cardiovascular risk factors, such as arterial hypertension, dyslipidemia, weight control, and maintaining healthy lifestyles. We have a lot of drugs for the treatment of DM2, and metformin is still the drug of first choice due to its low cost and proven effectiveness...
Subject(s)
Humans , Male , Female , /drug therapy , Metformin/therapeutic use , Administration, Oral , alpha-Glucosidases , Sulfonylurea Compounds/therapeutic use , Glycemic Index , Hypoglycemic Agents/administration & dosage , Incretins/therapeutic use , Glucagon-Like Peptide 1/agonists , Thiazolidinediones/therapeutic useABSTRACT
Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner. We investigated whether a PPARalpha agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.
Subject(s)
Animals , Male , Rats , Blood Glucose/metabolism , Body Weight/drug effects , Diabetes Mellitus, Experimental/drug therapy , Drug Therapy, Combination , Feeding Behavior/drug effects , Fenofibrate/pharmacology , Glucagon-Like Peptide 1/agonists , Glucose/metabolism , Glucose Tolerance Test , Homeostasis/drug effects , Immunohistochemistry , Injections, Intraperitoneal , Insulin-Secreting Cells/drug effects , Lipid Metabolism/drug effects , Metformin/pharmacology , Peptides/administration & dosage , Receptors, Glucagon/metabolism , Venoms/administration & dosageABSTRACT
En los últimos años se reconoce un nuevo mecanismo involucrado en la fisiopatología de la Diabetes Mellitus tipo 2: el déficit de producción y/o acción de las incretinas. Las incretinas son enterohormonas que estimulan la secreción de insulina en respuesta a la ingesta de nutrientes. Glucagon like peptide-1 (GLP1) y Polipéptido insulinotrópico glucosa dependiente (GIP) son las principales incretinas descubiertas hasta hoy. Ambas presentan también efecto trófico sobre las células beta de los islotes pancreáticos. GLP-1 presenta otras acciones como son la inhibición de la secreción de glucagón, enlentecimiento del vaciamiento gástrico e inhibición del apetito. Ambas incretinas son rápidamente clivadas por la enzima dipeptidil peptidasa 4 (DPP-4). Nuevas drogas como los incretinomiméticos, análogos y los inhibidores de DPP-4 se presentan como una terapéutica prometedora para los pacientes con diabetes tipo 2. Conflicto de intereses: Dr. León Litwak - Miembro del Board Latinoamericano de Eli Lilly y Sanofi Aventis - Miembro del Board Nacional de los laboratorios Novo Nordisk, Novartis, GlaxoSmithKline, Sanofi Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Investigador principal de protocolos pertenecientes a Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKline, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amger, Roche, Minimed, Quintiles - Conferencista de los laboratorios mencionados.
Two main pathophysiological mechanisms are currently involved in Type 2 Diabetes (T2DM), insulin resistance and impairment of beta cell function. However, in recent years a new mechanism was reported: a significant decrease in incretins production and/or action. Incretins are gastrointestinal hormones whose main action is stimulating insulin secretion in response to nutrients. The best known incretins are glucagon like peptide-1 (GLP-1) and Gastric insulinotropic peptide (GIP). GLP-1 and GIP not only increase insulin secretion, but also decrease glucagon secretion, slow gastric emptying and reduce apetite, generating weight loss. Both incretins are rapidly clived by the enzyme dipeptidil peptidase 4 (DPP4). In order to emulate incretins action, several drugs were developed: GLP-1 receptor agonists, GLP-1 mimetics, and DPP4 inhibitors. All of them seem to became a very promising tool for the treatment of T2DM. Financial Interests: Dr. León Litwak - Member of the Latin American Board of Eli Lilly and Sanofi Aventis - Member of the National Board of the following laboratories: Novo Nordisk, Novartis, GlaxoSmithKlein Sanofi, Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Principal Investigator of Protocols from: Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKlein, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amgen, Roche, Minimed, Quintiles - Lecturer for the former laboratories.