GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

Practical and conceptual issues of clinical trial registration for Brazilian researchers / Aspectos práticos e conceituais do registro de ensaios clínicos para pesquisadores brasileiros

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.

CONTEXTO E OBJETIVO: O registro dos ensaios clínicos é pré-requisito para publicação em revistas científicas de prestígio. Recentes mecanismos regulatórios brasileiros também exigem o registro de determinados ensaios clínicos na plataforma nacional (Registro Brasileiro de Ensaios Clínicos, ReBEC). Porém há pouca informação disponível sobre questões práticas envolvidas no processo de registro. Este trabalho discute a importância do registro de ensaios clínicos e aspectos práticos envolvidos nesse processo. DESENHO DE ESTUDO E LOCAL: Estudo descritivo realizado por pesquisadores de um programa de pós-graduação em uma universidade pública em São Paulo, Brasil. MÉTODOS: Informações foram obtidas em plataformas de registro de ensaios clínicos, referências dos artigos encontrados e websites (última busca: setembro, 2014) sobre os seguintes temas: definição de ensaio clínico, história, objetivo e importância das plataformas de registro, quais informações devem ser registradas e o processo de registro. RESULTADOS: O registro de ensaios clínicos visa evitar viés de publicação e é exigido por revistas brasileiras disponíveis no LILACS, SciELO e revistas afiliadas ao Comitê Internacional de Editores de Revistas Médicas (ICMJE). Recentes normas brasileiras exigem que todos os ensaios clínicos (fases I a IV) envolvendo novos medicamentos no país sejam registrados no ReBEC. São discutidos os prós e contras da utilização de diferentes bases de registro de ensaios clínicos. CONCLUSÃO: O registro de ensaios clínicos é importante e atualmente existem vários mecanismos que obrigam seu uso. Quando forem escolher em qual plataforma registrar seu ensaio clínico, os pesquisadores devem levar em consideração quais são as normas nacionais e as exigências para publicação.

Practical and conceptual issues of clinical trial registration for Brazilian researchers.

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.