As GLP-1 therapies capture global attention for their success in treating obesity and type 2 diabetes, a new white paper from ICON explores how clinical trial design must evolve to keep pace with their expanding therapeutic potential. Based on insights from a recent survey and authored by leaders in internal medicine, cardiology, and gastroenterology, the paper identifies both opportunities and operational challenges in designing trials that support multi-indication outcomes.

In this Q&A, Dr Simon Bruce, Dr Jack Martin, and Dr Alan Baldridge—senior figures within ICON’s drug development solutions division—discuss how sponsors can adapt to the shifting landscape. They explore the role of adaptive designs, the promise of master protocols, and the importance of patient-centric strategies in building more inclusive, efficient, and forward-looking trials. With a particular focus on GLP-1-based therapies, the experts outline how early feasibility planning, biomarker integration, and digital tools are shaping the future of metabolic research.

What steps can sponsors take today to design trials better suited for multi-indication goals?

As obesity trials increasingly intersect with conditions like type 2 diabetes, MASH and cardiovascular disease, sponsors are rethinking trial design for multi-indication value. Early inclusion of biomarkers related to short-term weight loss or insulin sensitivity can support broader proof of concept. Adaptive designs aid dose selection and early signal detection across related pathways. In later phases, Bayesian borrowing and shared or historical controls can maximise data utility, especially where placebo use is limited. Master protocols, though underused in metabolic disease, enable cohort expansion, shared infrastructure and aligned data across indications. While complex, these approaches become feasible with experienced partners who can tailor strategies and guide practical implementation.

How is ICON addressing the apparent hesitation around adaptive or master protocol designs?

Despite growing interest, many sponsors remain cautious about adaptive and master protocols, citing regulatory and operational concerns. At ICON, we see that hesitation often stems from uncertainty, not resistance. We help de-risk these models through scenario-based planning and early strategic consultation. For adaptive trials, we guide sponsors in selecting fit-for-purpose elements like interim dose selection using short-term weight loss, related biomarkers or tolerability signals. We also advise on leveraging biomarkers and comorbidity surrogates to support subgroup analyses. For master protocols, we assess feasibility, define operational efficiencies and support modular, cross-indication trial infrastructures. Our approach includes justifying shared controls or historical data use as placebo arms become less viable. Rather than pushing a fixed model, ICON helps sponsors tailor innovation to their specific risk profile, resource limits and regulatory path—ensuring the design serves the program, not vice versa.

Can you share early success stories from your Centre for Obesity or pilot sites?

ICON’s Centre for Obesity consolidates knowledge across the company for all phases of obesity asset development. In early clinical development, we have successfully incorporated obese and overweight patient cohorts in multiple ascending dose studies with the same enrolment rates as with healthy subjects. This allowed one large sponsor to make a clear no-go decision on an early oral GLP-1 asset, and another sponsor to quickly complete their Phase 1 drug-drug interaction and renal impairment studies for another oral GLP-1 asset.

To mitigate growing competition for patients, ICON uses an AI-enabled multi-source site feasibility database, as well as our wholly owned Accellacare site network to conduct ongoing feasibility assessments and maintain rapid recruitment for obesity studies. To date, the network has recruited almost 4,000 patients into obesity trials, surpassing targets by about 30% with retention rates of approximately 95%. We also conducted one of the largest GLP-1 receptor agonist (RA) Phase 3b outcome trials with over 97% patient retention up to 7 years.

What are the most promising new indications for GLP-1-based therapies beyond weight loss and diabetes?

GLP-1 RAs show great promise in treating heart disease, which remains the number one cause of death worldwide. This class of agents has recently been demonstrated to reduce major cardiac events in high-risk obese patients without diabetes, in addition to their long-recognised capacity to reduce cardiac events in type 2 diabetes. The benefits of GLP-1 RAs and dual-integrin agonists in heart failure and renal disease further support the great potential for GLP-1 RAs to treat indications across the cardiovascular-kidney-metabolic space.

Emerging data support the benefits of GLP-1 RAs in neurodegenerative and addictive disorders as well, but continued research in these areas will require further understanding of the use of these agents in lean patients. Further work is also necessary to explore the potential benefits of incretin agonists on arthritis, cancer and other inflammatory and age-related disorders.

How are patient voices being incorporated into trial designs for these new therapies? 

Many patients with obesity and diabetes are actively working and caring for children or other family members. Accommodating these responsibilities, such as through decentralised or hybrid trial designs, is essential to reducing the patient burden of clinical trial participation. Patient engagement early on in protocol development is required to customise the study assessments to meet these needs. This includes feedback on the use of connected devices for remote data acquisition without excess burden. Patient input is also needed on messaging that will be provided to study participants related to study risks and perceived benefits. In this process it is essential to incorporate feedback from a diverse patient sample. Men and underserved minority populations have traditionally been underrepresented in obesity research. Incorporating the voice of these populations and customising the trial design to meet their needs is required to drive increased participation.