ABSTRACT
The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.
ABSTRACT
Introducción: Recientemente se han descubierto nuevos medicamentos para el tratamiento de la diabetes tipo 2, con novedosos mecanismos de acción y menos efectos adversos. Dentro de ellos tenemos los análogos del péptido similar al glucagón tipo 1. Objetivo: Explicar la evidencia existente sobre los efectos del tratamiento con agonistas del receptor del péptido similar al glucagón tipo 1 en las personas con obesidad y diabetes mellitus tipo 2. Material y Métodos: Se realizó una revisión sistemática que incluyó estudios de los efectos de los agonistas del receptor del péptido similar al glucagón tipo1 como tratamiento en personas mayores de 12 años con obesidad y diabetes tipo 2. Se realizó una síntesis narrativa formal de los datos recogidos, no se realizó una síntesis estadístico formal. La calidad de evidencia para cada desenlace se determinó, según la metodología Grading of Recommendations Assessmet, Developmet and Evaluation. Resultados: La evidencia disponible demuestra que los agonistas del receptor del péptido similar al glucagón tipo 1, lograron una mayor disminución del peso corporal (-7,0 por ciento vs -2 por ciento) y de las cifras de hemoglobina glucosilada (HbA1c) (-0,40 por ciento vs -0,10 %) respecto al grupo placebo. Además, de una mayor reducción de la cintura abdominal. Conclusiones: La evidencia analizada muestra que los fármacos del tipo agonistas del receptor del péptido similar al glucagón tipo 1 tienen efectos beneficiosos en el tratamiento de las personas con obesidad y diabetes, disminuyendo el peso corporal y los valores de glucemia(AU)
Introduction: New drugs with novel mechanisms of action and fewer adverse effects have recently been discovered for the treatment of type 2 diabetes. Among them are glucagon-like peptide-1 analogues. Objective: To explain the existing evidence of the effects of treatment with glucagon-like peptide-1 receptor agonists in people with obesity and type 2 diabetes mellitus. Material and Methods: We conducted a systematic review that included studies on the effects of glucagon-like peptide -1 receptor agonists for the treatment of people older than 12 years with obesity and type 2 diabetes. A formal narrative synthesis of the collected data was performed, whereas a formal statistical synthesis was not performed. The quality of evidence for each outcome was determined according to the Grading of Recommendations Assessment, Development and Evaluation method. Results: The available evidence shows that glucagon-like peptide -1 receptor agonists achieved a greater reduction in body weight (-7,0 percent vs -2 percent) and glycosylated hemoglobin (HbA1c) (-0,40 percent vs -0,10 percent) compared to the placebo group. In addition, there was a greater reduction in abdominal waist circumference. Conclusions: The evidence analyzed shows that glucagon-like peptide -1 receptor agonists have beneficial effects in the treatment of people with obesity and diabetes, reducing body weight and glycemia values(AU)
Subject(s)
Humans , Male , Female , Glycated Hemoglobin , Diabetes Mellitus, Type 2 , Reference Drugs , Waist Circumference , Obesity , Methodology as a SubjectABSTRACT
Resumen La prevalencia de diabetes mellitus tipo 2 (DM2) está en aumento, generando un gran impacto tanto a nivel individual como en salud pública. Cerca de la mitad de los pacientes con DM2 sufren un deterioro de la función renal, por esto la nefroprotección resulta de fundamental importancia. El conjunto de evidencia que cambió del enfoque terapéutico glucocéntrico al cardiorrenometabólico en la DM2 motivó la inclu sión en las recomendaciones internacionales de nuevas terapias con beneficios cardiovasculares y renales. Los agonistas del receptor del péptido similar al glucagón tipo 1 (GLP-1) tienen efectos favorables sobre la función renal y sus posibles acciones protectoras son multifactoriales, más allá del control glucémico. Estos beneficios han sido demostrados en los estudios clínicos de eficacia y seguridad, así como también en los estudios de re sultados cardiovasculares y de vida real. En esta revisión narrativa se describen los efectos directos e indirectos de estas moléculas, así como su evidencia en los principales estudios clínicos (LEADER, SUSTAIN 6 y REWIND) y de vida real que demuestran sus efectos beneficiosos sobre la función renal e introduce la expectativa de los resultados futuros de los estudios en curso con objetivos renales.
Abstract The prevalence of type 2 diabetes mellitus (DM2) is increasing, generating a great impact both at individual and public health level. Nearly half of the patients with DM2 develop impaired renal function, so nephron-protection is highly important. The robust body of evidence that shifted the therapeutic focus from glycemic to cardio-renal metabolic therapy in DM2 led to the inclusion of new therapies with cardiovascular and renal benefits in international guidelines. Type 1 glucagon (GLP-1) receptor agonists have showed favorable effects on renal function and their potential protective actions are multifactorial, beyond glycemic control. These benefits have been demonstrated in efficacy and safety clini cal studies, as well as in cardiovascular outcomes and real-life studies. This comprehensive review describes the direct and indirect effects of these molecules, as well as evidence obtained from pivotal clinical (LEADER, SUSTAIN 6 and REWIND) and real-life studies demonstrating their beneficial effects on renal function, and also introduces expectations of future results from ongoing studies with renal endpoints.
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Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.
ABSTRACT
Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.
ABSTRACT
La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.
Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.
Subject(s)
Humans , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Chemotherapy, Adjuvant , Glucagon-Like Peptide 1/therapeutic use , Sodium-Glucose Transporter 2/antagonists & inhibitors , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Metformin/therapeutic useABSTRACT
Type 2 diabetes is closely linked with obesity. Obesity is associated with risk of both development and progression of type 2 diabetes, as well as cardiovascular disease. Although lifestyle modifications aimed at prompting weight reduction are cornerstone therapies in managing type 2 diabetes, weight reduction remains challenging for overweight and obese patients with type 2 diabetes. A shift in the approach to weight management in patients with type 2 diabetes is clearly needed. Pharmacotherapy should be considered as a realistic treatment option for patients with type 2 diabetes who cannot lose weight with health behavior modification alone. This review is focused on current pharmacotherapies for obesity to support the glycemic and weight loss goals of obese people with type 2 diabetes.