RESUMO
BACKGROUND: To determine the effectiveness, persistence of use, adverse reactions, interactions of orlistat and liraglutide taken for weight loss by a group of obese patients in Colombia. RESEARCH DESIGN AND METHODS: A retrospective follow-up study of a cohort of patients with obesity treated with orlistat or liraglutide. Sociodemographic, clinical, and pharmacological variables were identified. The effectiveness for weight loss at 12-16 and 52 weeks, persistence of use, and safety were determined. RESULTS: A total of 294 patients were followed up. At 12-16 weeks after starting orlistat and liraglutide, weight losses of -1.2kg (p=0.002) and -4.1kg (p<0.001) were observed, respectively, and at 52 weeks, reductions of -1.6kg (p=0.208) and -7.8kg (p<0.001) were observed. A total of 8.8% and 31.3% of patients treated with orlistat and liraglutide, respectively, persisted with treatment 1 year after initiation. A total of 17.3% had adverse drug reactions. Older adults with grade II or III obesity who performed physical activity and those treated with liraglutide were more likely to have lost at least 5% of their body weight at 12-16 weeks. CONCLUSION: Orlistat and liraglutide users presented weight loss at 12-16 weeks. However, this effect was greater and sustained with liraglutide, especially when combined with physical activity.
Assuntos
Fármacos Antiobesidade , Liraglutida , Humanos , Idoso , Orlistate/efeitos adversos , Liraglutida/efeitos adversos , Fármacos Antiobesidade/efeitos adversos , Estudos Retrospectivos , Seguimentos , Lactonas/efeitos adversos , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
Liraglutida e terapia padrão (modificação no estilo de vida, com dieta e prática regular de exercícios), como opção disponível no Sistema Único de Saúde. Indicação: Tratamento da obesidade. Pergunta: Liraglutida, comparada à terapia padrão, é mais eficaz e segura para promover redução do peso em pessoas adultas com obesidade? Métodos: Revisão rápida de evidências, revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática que atendeu aos critérios de inclusão. Conclusão: Liraglutida em dose ≤ 1,8 mg e em dose > 1,8 mg, comparadas a placebo (com terapia padrão) promoveram redução estatisticamente significativa de peso (-2,99 kg e -4,55 kg, respectivamente) e maior risco relativo de descontinuação do tratamento devido a efeitos adversos, com alta certeza de evidência para esses desfechos, além de maior risco relativo de náusea e de vômitos
Liraglutide and standard therapy (lifestyle modification, diet and regular exercise), as a option available in the Brazilian Public Health System. Indication: Treatment of obesity. Question: Is Liraglutide, compared to standard therapy, more effective and safer for weight reduction in obese adults? Methods: Rapid review of evidence, overview of systematic reviews, with a bibliographic search in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Results: A unique systematic review that met the inclusion criteria was selected. Conclusion: Liraglutide at a dose ≤ 1.8 mg and at a dose > 1.8 mg, compared to placebo (and standard therapy) induced statistically significant weight reduction (-2.99 kg and -4.55 kg, respectively) and greater relative risk of treatment discontinuation due to adverse effects, with high certainty of evidence, and greater relative risk of nausea and vomiting
Assuntos
Humanos , Fármacos Antiobesidade/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Liraglutida/efeitos adversos , Revisões Sistemáticas como AssuntoAssuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Peso Corporal/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/agonistas , Sobrepeso/tratamento farmacológico , Liraglutida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Obesidade/tratamento farmacológico , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Placebos/administração & dosagem , Estados Unidos , Esquema de Medicação , Redução de Peso , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Resultado do Tratamento , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Sobrepeso/terapia , Liraglutida/efeitos adversos , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Obesidade/terapiaRESUMO
CONTEXT: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. OBJECTIVE: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. DATA SOURCES: We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. STUDY SELECTION: Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. DATA EXTRACTION: Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA SYNTHESIS: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76-1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48-2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. CONCLUSIONS: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.
Assuntos
Neoplasias da Mama/induzido quimicamente , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/efeitos adversos , Adulto , Neoplasias da Mama/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Exenatida/efeitos adversos , Feminino , Humanos , Liraglutida/efeitos adversos , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Risco , Fatores de RiscoRESUMO
BACKGROUND: Cardiovascular outcomes trials (CVOTs) have assessed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on major adverse cardiovascular events (MACE) and mortality in high cardiovascular (CV) risk populations. Observational research can provide complementary evidence about these effects in unselected populations. AIM: To systematically review retrospective observational cohort studies conducted in electronic healthcare databases (EHDs) assessing GLP-1 RAs´ effects on MACE and/or hospitalisation for heart failure (HHF) and/or all-cause mortality in Type 2 diabetes mellitus (T2DM) patients. METHODS: We systematically searched studies meeting inclusion criteria, compared design, methods and population characteristics, assessed risk for bias and did a meta-analysis (MA) using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). RESULTS: Sixteen studies included 285,436 T2DM patients exposed to GLP-1 RAs (exenatide bid, liraglutide, lixisenatide, long-acting exenatide), n ranged from 219 to 160,803 patients. Comparators included: no exposure, other antidiabetic medications (OADs), combined OADs, canagliflozin or multiple comparators. Ten studies estimated all-cause mortality, hazard ratios (HRs) ranged from 0.17 (95% CI 0.02-1.22) to 1.29 (95% CI 0.54-3.13). Thirteen studies assessed cardiovascular events and/or MACE; HRs ranged from 0.27 (95% CI 0.14-0.53) to 1.11 (95% CI 0.99-1.24). Eight studies assessed HHF, HRs ranged from 0.12 (95% CI 0.02-0.66) to 1.64 (95% CI 1.28-2.13). Excluding two studies because of temporal bias, we obtained pooled estimates for all-cause mortality: HR 0.63 (0.44-0.89), CV outcomes HR 0.84 (0.75-0.94) and HHF; HR 0.94 (0.78-1.14), (high between-study variability: I2 = 83.35%; I2 = 70.3%; and I2 = 90.1%, respectively). CONCLUSION: Pooled results of EHDs' studies assessing GLP-1 RAs effects favoured GLP-1 RAs for all-cause mortality and MACE while were neutral for HHF. Results should be interpreted cautiously because of studies' substantial heterogeneity and limitations of observational research.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/mortalidade , Hipoglicemiantes/efeitos adversos , Estudos de Coortes , Diabetes Mellitus Tipo 2/mortalidade , Exenatida/efeitos adversos , Insuficiência Cardíaca/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Liraglutida/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the safety, tolerability, and pharmacokinetics of liraglutide in adolescents with obesity. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial. Twenty-one subjects, aged 12-17 years and Tanner stage 2-5, with obesity (body mass index [BMI] corresponding to both a BMI ≥95th percentile for age and sex and to a BMI of ≥30 kg/m2 for adults; additionally, BMI was ≤45 kg/m2) were randomized (2:1) to receive 5 weeks of treatment with liraglutide (0.6 mg with weekly dose increase to a maximum of 3.0 mg for the last week) (n = 14) or placebo (n = 7). The primary endpoint was number of treatment-emergent adverse events (TEAEs). Secondary endpoints included safety measures, and pharmacokinetic and pharmacodynamic endpoints. RESULTS: All participants receiving liraglutide, and 4 receiving placebo (57.1%), had at least 1 TEAE. The most common TEAEs were gastrointestinal disorders. No severe TEAEs, TEAE-related withdrawals, or deaths occurred. Twelve hypoglycemic episodes occurred in 8 participants receiving liraglutide and 2 in 1 participant receiving placebo. No severe hypoglycemic episodes were reported. Liraglutide exposure in terms of trough concentration increased with dose, although dose proportionality was confounded by unexpectedly low trough concentration values at the 2.4 mg dose. Exposure in terms of model-derived area under the plasma concentration time curve from 0 to 24 hours after dose in steady state was similar to that in adults with obesity. CONCLUSIONS: Liraglutide had a similar safety and tolerability profile compared with adults when administered to adolescents with obesity, with no unexpected safety/tolerability issues. Results suggest that the dosing regimen approved for weight management in adults may be appropriate for use in adolescents. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01789086.
Assuntos
Hipoglicemia/induzido quimicamente , Liraglutida/farmacocinética , Liraglutida/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Adolescente , Área Sob a Curva , Índice de Massa Corporal , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Hipoglicemia/epidemiologia , Injeções Subcutâneas , Liraglutida/efeitos adversos , Masculino , Dose Máxima Tolerável , Segurança do Paciente , Obesidade Infantil/diagnóstico , Valores de Referência , Medição de Risco , Resultado do TratamentoRESUMO
EL FÁRMACO: Liraglutide (Lg) pertenece a una clase de hipoglucemiantes que tiene como mecanismo de acción la estimulación del receptor del péptido símil glucagón 1 (GLP-1), promoviendo la liberación de insulina dependiente de glucosa e inhibiendo la secreción de glucagón. Además retrasa el vaciado gástrico y disminuye el apetito. En animales se ha demostrado que puede preservar e incluso aumentar la masa de células beta pancreáticas. Lg está indicado para lograr control glucémico cuando no es posible hacerlo usando metformina o sulfonilureas a dosis máximas como monoterapia o combinadas o con biterapia con metformina y tiazolidinedionas. Los principales efectos adversos son gastrointestinales (diarrea, dolor abdominal, vómitos, náuseas, constipación) La hipoglucemia se observa cuando se realiza tratamiento asociado con sulfonilureas. Se administra a través de un inyector tipo lapicera que contiene 18 mg, las dosis varían entre 0,6 a 1,8 mg y se aplica en forma SC. BÚSQUEDA BIBLIOGRÁFICA: Se realizó una búsqueda en tripdatabase.com, base de datos CRD y MEDLINE. Se consultaron las recomendaciones de la Asociación Americana de Diabetes. RESULTADOS: Informe de ETS del National Institute of Clinical Excellence y guía de utilización del fármaco: Liraglutide for the treatment of type 2 diabetes mellitus. Las fuentes que utilizó el informe son 6 estudios provistos por el fabricante (LEAD-1, LEAD-2, LEAD-4, LEAD-5, LEAD-6 y el studio 1860) Los estudios tuvieron un seguimiento de 26 semanas, y algunos tuvieron una fase de seguimiento abierta. El punto final a evaluar fue el cambio en la HbA1C y los puntos secundarios incluían el porcentaje de pacientes que alcanzaron HbA1C menor a 7%, porcentaje de pacientes con HbA1C menor a 6,5% y cambio promedio del peso, y la tolerancia a los efectos adversos. CONCLUSIONES Y RECOMENDACIONES: La evidencia señala que liraglutide es eficaz en disminuir la HbA1C y tiene un perfil favorable con respecto a la disminución relativa de peso en comparación con otros hipoglucemiantes. Presenta un perfil de seguridad aceptable con reacciones adversas gastrointestinales principalmente. Sin embargo dado que no hay claras ventajas de liarglutide con respecto a otros hipoglucemiantes su papel se encuentra relegado a un segundo o tercer lugar de progresión en el tratamiento cuando no se pueden usar metformina o sulfonilureas o glitazonas o inhibidores DPP IV. En estas circunstancias su papel comparado con insulina tampoco resulta claro ya que también es inyectable, presenta un techo de dosis (para NICE de 1,2 mg) y, seguramente como otros hipoglucemiantes, resultará insuficiente y no evitará la necesidad de insulina con el paso del tiempo. No se recomienda su cobertura debido a que es un hipoglucemiante más entre otros, con la desventaja que es de administración SC, que no previene el deterioro de la función de la célula beta y que es incierto que su efecto sobre el peso pueda ser relevante en el largo plazo, sobre todo teniendo en cuenta que la mayoría de los pacientes requerirán insulina aunque sean obesos.