Francisco Jesús Gómez Delgado
Coordinator of the Vascular Risk Unit and head of the Internal Medicine Department at the University Hospital of Jaén, Associate Professor of Medicine at the University of Jaén and member of the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine
Article 1: Orforglipron
Is this a high-quality study?
“The fact that it is a clinical trial specifically designed for a particular objective ensures the highest possible rigour. Specifically, it is a phase 3b, randomised, double-blind, placebo-controlled trial, with two well-defined cohorts from previous incretin-based treatments, in which the sample size has been calculated to enable the analysis and demonstration of the primary and secondary endpoints defined for this study.”
What are its limitations?
“The main limitation is that it conducts a head-to-head comparison and does not compare orforglipron with continued treatment with semaglutide or tirzepatide, as was done in the SURMOUNT-5 clinical trial from which these patients originated. Furthermore, the study lasts only 52 weeks, which limits our full understanding of its long-term efficacy and safety.”
What are its implications and how does it fit with existing evidence?
“This study reinforces the idea that obesity is a chronic condition requiring a long-term therapeutic approach using the various tools available, including maintenance therapies with orally administered incretins, which are potentially more scalable and acceptable to many patients.”
Article 2: Akkermansia muciniphila pasteurised
Is this a high-quality study?
“This study, as in the previous case, is a randomised, placebo-controlled trial, so we can affirm its methodological robustness for a clinical proof-of-concept. Furthermore, it incorporates biomarkers and mechanisms of interest in understanding metabolic health, such as the gut microbiota, adipose tissue, and lipid and glucose metabolism.”
What are its limitations?
“On the other hand, its sample size is small, the follow-up period is short, and the demonstrated effect on body weight is limited. Furthermore, it does not include other active comparators or biological models that would allow the observed benefit to be confirmed or clarified more precisely.”
What are its implications and how does it fit with existing evidence?
“In this regard, it clearly supports the hypothesis and the role played by our gut microbiota, depending on its profile, in phenomena such as inflammation, dyslipidaemia or diabetes. Similarly, this study identifies the gut microbiota as a real therapeutic target in the management of obesity. Furthermore, it is proposed as a complementary tool to supplement pharmacological, nutritional and behavioural strategies, which makes it an interesting option.”