Abstract:
The unprecedented weight loss efficacy of GLP-1-based therapies has fueled a rapidly proliferating market for GLP-1-based obesity treatments and spurred increased drug development for new weight loss agents with potential competitive advantages over existing therapies. We analyzed the total number of clinical trials from Phase 1 to 4 registered in clinicaltrials.gov registered from 2013 to 2024, divided in 3 periods: period 1 (P1[2013 to 2016]), period 2 (P2[2017 to 2020]), and period 3 (P3 [2021 to 2024]. Our comparison between periods demonstrated a 68.1% increase in trials of medicinal products for or weight loss in P3 versus P2. Conversely, there was a 12.3% reduction in trials between P1 and P2. The marked positive trend reversal in P3 coincides with the publication of landmark GLP-1 Phase 3 trials, supporting the evidence that GLP-1-based therapies are key drivers of clinical research into weight loss in obese diabetic and non-diabetic populations, as well as their complications and comorbidities.
The increasing research into new weight loss treatments has highlighted BMI limitations and the need for more precise definitions of obesity to facilitate personalized and precision treatments for diverse obesity geno- and phenotypes. While BMI remains the regulatory gold standard for defining study populations, the impact of the Lancet Commission Recommendationson future clinical trial endpoints in Cardiovascular, Kidney, and Metabolic Syndrome trials remains to be determined1,2.
Beyond BMI, there is a growing need to evaluate weight loss agents' effects on body composition (BC), such as bone density, skeletal muscle volume, strength and function, and organ-specific changes in adipose tissue (liver, heart, pancreas, and kidney). Understanding the differential effects of new weight loss agents on BC is particularly relevant in pediatric, adolescent, and elderly populations. Incorporating BC endpoints into study design may allow product differentiation in an increasingly crowded market.
The proven safety and success of new GLP-1-based obesity therapies have resulted in new challenges in the design, conduct, and oversight of weight loss clinical trials. The multifaceted benefits beyond weight loss and glycemic control of newer weight-loss agents are driving new therapy targets, necessitating multiple metabolic endpoints to enhance future protocol efficiency.
The rapid expansion in obesity research presents new challenges and exciting opportunities for competitive and cost-effective new drug development. This review highlights the emerging frontiers of obesity clinical research, and we share our insights and experiences on the impact of the rapidly expanding pipeline of obesity clinical trials on the design and execution of weight-loss protocols in persons living with obesity.
