RESUMO
Background: Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting. Methods: An observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events. Results: 67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline. Conclusions: This real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Insulina/uso terapêutico , Insulina de Ação Prolongada , LiraglutidaRESUMO
This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Dipeptídeos , Glutamina , Hipoglicemia , Insulina de Ação Prolongada , Insulinas , Animais , Glicemia/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Dipeptídeos/efeitos adversos , Glucose/metabolismo , Glutamina/farmacologia , Homeostase , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos , Insulina de Ação Prolongada/farmacologia , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Triglicerídeos/efeitos adversosRESUMO
Antecedentes: En el tratamiento de la diabetes se buscan insulinas de acción más prolongada y con menores tasas de hipoglicemias. Objetivo. Uso del análogo de insulina de acción ultralenta degludec en diabéticos tipo 1 (DM1) tratados previamente con glargina. Pacientes y método: Se observaron 230 DM1 durante 18 meses, promedio de edad 34 años y de diagnóstico 14 años, registrándose parámetros clínicos, bioquímicos, hipoglicemias y requerimientos de insulina (U/kg/peso), en régimen basal/bolo, con degludec y ultra-rápida precomidas. Degludec se ajustó quincenalmente. Resultados: A los 3 meses, la glicemia de ayunas disminuyó de 253mg/dl (243-270) a 180 mg/dl (172- 240), (p< 0,05); a los 6 meses a 156 mg/dl (137-180) (p< 0,05), a los 12 meses a 151 mg/dl (50-328) (p< 0,001) y a los 18 meses 150 (50-321) (p<0,001). La HbA1c, inicialmente de 10,6% (10,3-12,2) bajó a los 3 meses a 8,7% (8,2-11,1) (p< 0,05), a 6 meses a 8,3% (8,0-9,6) (p<0,05), a los 12 meses subió 9,0% (5,9-14,5) (p<0,001) y a los 18 meses 9,0% (5,9-14,6) (p<0,001). La dosis de degludec fue 0,5 U/kg/peso a los 18 meses. Hubo reducción de hipoglicemias: a los 3 meses 14 leves, 4 moderados 1 grave; a los 6 meses 8 leves, 2 moderados y ninguna grave; a los 12 meses 1 leve, y a los 18 meses 2 leves, 1 moderado y ninguna grave. Un 7,8% no presentó hipoglicemias. Conclusión: Degludec en DM1 mostró reducir las glicemias de ayunas y HbA1c, y menor número de hipoglicemias.
Background: In the treatment of diabetes, longer-acting insulins with lower rates of hypoglycaemia are sought. Objective. Use of ultralow-acting insulin analog degludec in type 1 diabetic patients (T1D) previously treated with glargine. Patients and method: 230 T1D patients were observed during 18 months, average of age 34 years and of diagnosis 14 years, registering clinical, biochemical, hypoglycemia and insulin requirements (U / kg / weight), in basal / bolus regimen, with degludec and ultra-fast pre-meals. Degludec adjusted himself fortnightly. Results: At 3 months, the fasting glycemia decreased from 253 mg / dl (243-270) to 180 mg / dl (172 - 240), (p <0.05); at 6 months at 156 mg / dl (137-180) (p <0.05), at 12 months at 151 mg / dl (50-328) (p <0.001) and at 18 months 150 (50-321) ;(p <0.001). HbA1c, initially of 10.6% (10.3-12.2), decreased after 3 months to 8.7% (8.2 - 11.1) (p <0.05), to 6 months to 8 months, 3% (8.0-9.6) (p <0.05), at 12 months it rose 9.0% (5.9-14.5) (p <0.001) and at 18 months 9.0 % (5.9-14.6) (p <0.001). The dose of degludec was 0.5 U / kg / weight at 18 months. There was reduction of hypoglycemia: at 3 months, 14 mild, 4 moderate, 1 severe; at 6 months 8 mild, 2 moderate and none serious; at 12 months 1 mild, and at 18 months 2 mild, 1 moderate and none serious. 7.8% did not present hypoglycemia. Conclusion: Degludec in T1D patients showed to reduce fasting glycemia and HbA1c, and lower number of hypoglycemia.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Insulina de Ação Prolongada/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas/análise , Seguimentos , Diabetes Mellitus Tipo 1/sangue , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversosRESUMO
Diabetes mellitus is a true pandemic; type 2 diabetes in particular, with its progressive nature, constitutes a serious health problem. Despite advances and innovations in treatment, it continues to generate high morbidity and mortality. Many patients do not achieve their metabolic control objectives, due to clinical inertia, fear of hypoglycaemia, weight gain, the complexity of the treatment and the lack of adherence to it. Recently, the clinical results of the combined use of basal insulin and agonist receptor of the glucagon-like peptide type 1 (AR-GLP1) have been successfully evaluated. Therefore, the combined use of a basal insulin (insulin degludec) with an AR-GLP1 (liraglutide), in a single device (IdegLira), is proposed as an effective and safe therapeutic alternative for the treatment intensification in people with type 2 diabetes. IdegLira has shown greater reductions in HbA1c compared to its individual components, with a low risk of hypoglycaemia and weight loss, both in insulin naïve patients and in those previously insulinized. In this review we describe the pharmacology, the rational of the combination and the most relevant clinical evidence on IdegLira safety and efficacy.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Liraglutida/administração & dosagem , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Quimioterapia Combinada , HumanosRESUMO
La diabetes mellitus es una verdadera pandemia; la diabetes tipo 2 en particular, con su carácter progresivo, constituye un grave problema de salud. A pesar de los avances e innovaciones en el tratamiento, continúa generando una alta morbimortalidad, debido a que muchos pacientes no logran los objetivos de control metabólicos, entre otras causas por la inercia clínica, el temor a la hipoglucemia, el aumento de peso, la complejidad del tratamiento y la falta de adherencia al mismo. En el último tiempo, se ha evaluado con éxito los resultados clínicos del uso combinado de insulina basal y agonistas del receptor del péptido similar al glucagón tipo 1 (AR-GLP1). Se propone, por lo tanto, el uso combinado de una insulina basal (insulina degludec) con un AR-GLP1 (liraglutida), en un único dispositivo (IdegLira), como una alternativa terapéutica eficaz y segura para la intensificación del tratamiento de las personas con diabetes tipo 2. IdegLira ha demostrado mayores reducciones de HbA1c comparado con sus componentes individuales, con un bajo riesgo de hipoglucemia y pérdida de peso, tanto en pacientes naive de insulina como en aquellos previamente insulinizados. En esta revisión se describe la farmacología, el racional de la combinación y la evidencia clínica relevante de la seguridad y eficacia de IdegLira.
Diabetes mellitus is a true pandemic; type 2 diabetes in particular, with its progressive nature, constitutes a serious health problem. Despite advances and innovations in treatment, it continues to generate high morbidity and mortality.Many patients do not achieve their metabolic control objectives, due to clinical inertia, fear of hypoglycaemia, weight gain, the complexity of the treatment and the lack of adherence to it. Recently, the clinical results of the combined use of basal insulin and agonist receptor of the glucagon-like peptide type 1 (AR-GLP1) have been successfully evaluated. Therefore, the combined use of a basal insulin (insulin degludec) with an AR-GLP1 (liraglutide), in a single device (IdegLira), is proposed as an effective and safe therapeutic alternative for the treatment intensification in people with type 2 diabetes. IdegLira has shown greater reductions in HbA1c compared to its individual components, with a low risk of hypoglycaemia and weight loss, both in insulin naïve patients and in those previously insulinized. In this review we describe the pharmacology, the rational of the combination and the most relevant clinical evidence on IdegLira safety and efficacy.
Assuntos
Humanos , Insulina de Ação Prolongada/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Liraglutida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Quimioterapia CombinadaRESUMO
INTRODUCTION: Degludec (IDeg) is an ultralong-acting insulin, with stable pharmacodynamic profile which leads to lower fluctuations in glucose levels. The effect of IDeg has not been specifically assessed in patients with unstable diabetes, defined as increased glycemic variability (GV). METHODS: A prospective before-after pilot study was conducted, including patients managed at Hospital Universitario San Ignacio in Bogotá, Colombia. The impact of the switch from a Glargine or Detemir insulin to a basal insulin regimen with IDeg for 12â¯weeks on GV measured by continuous glucose monitoring, on A1c levels, and on the incidence of episodes of global and nocturnal hypoglycemia was assessed in a group of patients with (coefficient of variationâ¯>34%) or without increased basal GV using a Generalised Estimating Equation (GEE) analysis. RESULTS: 60 patients with basal bolus therapy and history of hypoglycemia were included. 18 patients had High GV (HGV). In this group a significant reduction of 11.1% of CV (95% CI: 6.3, 15.9, pâ¯=â¯0.01) was found. GEE analysis confirmed a higher impact over time on patients with HGV (pâ¯<â¯0.001). The percentage of patients with at least 1 episode of hypoglycemia decreased from 66.6% to 22.2% (pâ¯=â¯0.02) and from 37.14% to 5.71% (pâ¯<â¯0.01) for global and nocturnal hypoglycemia, respectively. Changes were not significant in patients with low GV. A reduction of A1c was observed in both groups (pâ¯<â¯0.001). CONCLUSIONS: The results suggest that treatment with IDeg reduces GV, A1c levels and the incidence of global and nocturnal hypoglycemia events in patients with HGV, but not in patients with low GV.
RESUMO
AIM: The efficacy and safety of insulin degludec (IDeg), a new basal insulin with an ultra-long duration of action, was compared to sitagliptin (Sita) in a 26-week, open-label trial. METHODS: Insulin-naïve subjects with type 2 diabetes [n = 458, age: 56 years, diabetes duration: 7.7 years, glycosylated haemoglobin (HbA1c): 8.9% (74 mmol/mol)] were randomized (1 : 1) to once-daily IDeg or Sita (100 mg orally) as add-on to stable treatment with 1 or 2 oral antidiabetic drugs (OADs). RESULTS: Superiority of IDeg to Sita in improving HbA1c and fasting plasma glucose (FPG) was confirmed [estimated treatment difference (ETD) IDeg-Sita for HbA1c: -0.43%-points [95% confidence interval (CI): -0.61; -0.24, p < 0.0001] and for FPG: -2.17 mmol/l (95% CI: -2.59; -1.74, p < 0.0001)]. HbA1c < 7% (<53 mmol/mol) was achieved by 41% (IDeg) versus 28% (Sita) of patients, estimated odds ratio IDeg/Sita: 1.60 (95% CI: 1.04; 2.47, p = 0.034). There was no statistically significant difference in the rate of nocturnal confirmed hypoglycaemia between IDeg and Sita [0.52 vs. 0.30 episodes/patient-year, estimated rate ratio (ERR): IDeg/Sita: 1.93 (95% CI: 0.90; 4.10, p = 0.09)]. Rates of overall confirmed hypoglycaemia were higher with IDeg than with Sita [3.1 vs. 1.3 episodes/patient-year, ERR IDeg/Sita: 3.81 (95% CI: 2.40; 6.05, p < 0.0001)]. IDeg was associated with a greater change in body weight than Sita [ETD IDeg-Sita: 2.75 kg (95% CI: 1.97; 3.54, p < 0.0001)]. The overall rates of adverse events were low and similar for both groups. CONCLUSIONS: In patients unable to achieve good glycaemic control on OAD(s), treatment intensification with IDeg offers an effective, well-tolerated alternative to the addition of a second or third OAD.