Review title GLP-1 eficcacy in severely obese people: systematic review of individual patient data of clinical trials. Condition or domain being studied Obesity is a chronic condition in which increased body fat promotes adipose tissue dysfunction and metabolic consequences. Traditionally, obesity is characterized by the presence of a body mass index (BMI) 30 kg/m2 (variable definition, according to ethnic/genetic factors) and severe obesity is a definition that encompasses people living with a BMI40kg/m2. Clinical trials assessing the efficacy of GLP-1 receptor agonist drugs (GLP1-RA) have led to a shift in obesity pharmacotherapy, with mean weight loss percentages ranging from 8,0% (liraglutide) to 20,9% (tirzepatide). However, such evidence derives from enrolled populations with a mean BMI of 38kg/m2 at baseline and little is known about the efficacy of such drugs in very high BMI subgroups. Rationale for the review Clinical trials assessing the efficacy of GLP-1 receptor agonist drugs (GLP1-RA) have led to a shift in obesity pharmacotherapy, with mean weight loss percentages ranging from 8,0% (liraglutide) to 20,9% (tirzepatide). However, such information derives from enrolled populations with a mean BMI of 38kg/m2 at baseline and little is known about the efficacy of such drugs in very high BMI subgroups. Recent reports suggest an increase in worldwide population with BMI N10 kg/m2 (nearly 10% of the US population). The need to provide accurate information about treatment strategies is of interest because people with extremely high BMI have a higher risk of complications and death, and usually need therapy resources to become able to undergo surgical interventions. Subgroups of severe obesity are often underrepresented in clinical trials and current information about the efficacy of GLP1-RA treatment comes from aggregate data of a large range of BMI. The analysis of individual patient data may determine the effect size and time-to-event outcomes associated with the GLP1-RA therapy in severely obese subgroups. Review objectives Question: What is the efficacy and safety of GLP1-RA in treating obesity in severely obese people (40kg/m2 and above)? Aim: This review aims to determine the efficacy and safety of GL1-RA for weight loss in severe obesity (BMIN10kg/m2). Specific aims: • To describe the proportion of severely obese patients in pivotal clinical trials of GLP1-RA therapy for obesity; • To determine the size effect of GLP1-RA treatment on severely obese patients; • To describe time-to-event (weight loss) among severely obese patients subgroups treated with GLP1-RA; • To compare safety outcomes in severely obese patient subgroups according to distinct BMI ranges.