As obesity levels continue to rise, impacting millions globally, the quest for effective treatments has become a critical public health focus. The latest advances in drug development, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists, are revolutionising the treatment landscape. However, this progress doesn’t come without challenges.
A recent ICON survey of over 100 obesity drug development professionals sheds light on current trends, therapeutic approaches and the roadblocks ahead in combating obesity and its comorbidities. Here, we outline some of the key takeaways and considerations as we drive progress in this therapeutic area.
GLP-1 receptor agonists and the shift in obesity treatment
For decades, obesity treatment centred primarily on lifestyle modifications like diet, exercise and behavioural therapy. However, these methods often fall short in the long term, as many patients regain most of their lost weight within five years.
Bariatric surgery has provided an effective yet invasive alternative to lifestyle-only modifications, though it is only suitable for a small subset of patients. Past pharmacological approaches to treatment have also faced setbacks – take the serious cardiovascular issues associated with fenfluramine in the 1990s – highlighting the potential risks of some drugs.
Now, with GLP-1 receptor agonists, a new generation of obesity treatments is emerging. Drugs like semaglutide and tirzepatide are not only aiding weight loss but also showing promise in managing comorbidities such as cardiovascular disease and metabolic dysfunction-associated steatotic liver disease (MASLD. GLP-1 receptor agonists stimulate insulin production, curb appetite and slow gastric emptying, making them among the most effective anti-obesity agents available. In ICON’s survey, a majority of respondents expressed confidence in their organisations’ obesity treatment pipelines, signalling a promising future.
Embracing multi-indication therapies and obesity comorbidities
Obesity is rarely a standalone condition; it often coexists with issues like diabetes, cardiovascular disease and mental health conditions. Consequently, an integrated approach to obesity studies with multi-indication therapies that address these common comorbidities are gaining traction.
In ICON’s survey, the majority of respondents (64%) saw combination therapies as the future of obesity treatment while only 17% of respondents pointed to single therapies. Multi-indication research reflects this trend, with many respondents exploring obesity in conjunction with other therapeutic areas like diabetes (55%), other metabolic disorders (48%) and cardiovascular diseases (38%).
The multi-indication approach aligns with the complex biology of obesity, allowing researchers to tackle a spectrum of interlinked health issues. By addressing the root causes of obesity alongside associated conditions, these combination therapies could lead to more comprehensive and sustainable health outcomes.
Overcoming challenges in obesity drug development
Despite the advancements, obesity research and drug development face considerable clinical trial hurdles. Survey respondents ranked the top challenges as a lack of obesity-specific trial designs (39%), the need for long-term follow up (44%), and difficulty recruiting diverse patient populations (38%). Here’s how the industry is addressing each:
1. Innovative clinical trial design
Selecting the right clinical trial design is paramount to the success of any trial. Traditional trials may not be ideal for obesity studies, particularly those investigating multiple conditions. Innovative approaches like master protocols and basket trials allow researchers to test therapies across related indications, improving trial efficiency. This flexibility is essential for multi-indication obesity trials that aim to target interconnected health conditions.
2. Ensuring long term follow-up success
Long-term follow up (LTFU) data are vital for obesity drugs, particularly in proving their impact on related health events, such as heart disease. For instance, Novo Nordisk’s five-year SELECT trial demonstrated that Wegovy (semaglutide) reduced major cardiovascular events, setting a benchmark for other obesity treatments.
However, LTFUs add significant cost and complexity. To offset these challenges, sponsors can leverage efficiencies through patient-centric trial designs, such as hybrid and remote trials, which reduce participant burden and improve retention. Newer methods, including health data tokenisation, also support ongoing data collection from secondary sources like electronic health records.
3. Increasing diversity in obesity trial recruitment
Diversity in clinical trials is a growing priority, but obesity studies face unique obstacles. For instance, women constitute approximately 75% of obesity trial participants even though obesity rates are similar across genders. Racial and ethnic minorities are also underrepresented. To address these gaps, sponsors can use targeted, demographic-specific outreach strategies with innovative site identification and feasibility tools.
Digital health technologies, including wearables or apps, can ease and enhance the patient experience. This positively impacts retention and compliance rates by connecting, monitoring and engaging patients at every step of the clinical trial journey with customised support services and patient-centred solutions. Specifically, respondents noted that survey respondents believe that reducing patient burden (33%) and monetary incentives (30%) had the greatest potential impact on improving diverse patient recruitment.
The path ahead: Future trends and opportunities for obesity treatment
With obesity rates projected to reach one billion cases by 2030, the need for effective interventions is urgent. Fortunately, advances in drug development, especially in combination therapies, and innovative trial strategies provide reasons for optimism. Over half of ICON’s survey respondents expressed confidence in their organisation’s pipeline for obesity treatments, underscoring the industry’s dedication to improving outcomes for patients worldwide.
As the field continues to evolve, a collaborative approach that integrates innovative drug development, personalised care and patient-centric trials may be the key to combating this global health challenge. With the right strategies, the future of obesity treatment holds promise for both improving health and reducing the societal burden of this complex disease.
