From Dropout to Retention: Solving the Patient Engagement Gap in Obesity Trials

Incretin-based anti-obesity medications (AOMs) have reshaped expectations for pharmacologic weight management. They deliver substantial and sustained weight loss, improve glycemic control, and favorably shift cardiometabolic risk. Yet, the clinical trials that bring these therapies to market still face a persistent challenge: many participants stop treatment early. 

Across major Phase 3 programs, attrition rates in the range of 15–30% are common, with gastrointestinal adverse events, perceived lack of efficacy, and logistical burden among the leading contributors. These discontinuations limit drug exposure, and the missing data may reduce statistical power, and introduce bias into both efficacy and safety analyses. All issues that ICH E9(R1) explicitly flags as critical intercurrent events. To generate reliable evidence in obesity trials, retention needs to be planned for from the outset, not addressed only after problems emerge. 

What the Evidence Tells Us About Retention 

Recent studies have examined which engagement strategies meaningfully reduce attrition in obesity trials. A systematic review of weight loss interventions across 57 studies and more than 7,500 participants highlighted three strategies with particularly compelling effects: 

1. Financial incentives reduced attrition by up to 43%, suggesting that addressing the opportunity costs of participation can materially influence a patient’s decision to stay in a trial.

    

2. Self-monitoring interventions reduced attrition risk by 41%, likely by increasing awareness of progress and reinforcing a sense of control over outcomes.

    

Multicomponent programs combining nutrition, physical activity, and psychological support reduced attrition by 33%, aligning with the reality that obesity is not a unidimensional condition and requires multi-dimensional support.

These findings are echoed in regulatory guidance: the FDA Guidance (2025) emphasizes the importance of incorporating scalable lifestyle-modification programs alongside pharmacotherapy in at least one Phase 3 trial.

Dietitian-led support provides another example of a high-yield, practical intervention. In Phase 3 programs involving more than 4,400 participants across 15 countries, structured dietitian support was associated with a median 1-year retention rate of 82%. Sites whose dietitians attended at least 11 teleconferences had a 32% lower dropout rate, underscoring that consistent support and frequent ‘touchpoints’ translate into improved participant retention.

Goal setting: More Than a Tick-box Exercise 

Goal setting is an established element of protocol design; however, its effectiveness is contingent on thoughtful and robust implementation. Our analysis of 24 studies (including 21 randomized trials) showed that goal-setting interventions in weight, diet, and physical activity resulted in the greatest impact on behavior change.  Many patients showed clear improvements in behaviors despite not achieving clinically meaningful weight loss (>5% of body weight at the study endpoint.

We identified several patterns that are directly relevant for obesity trial design:

1. Adaptive, percentile-based goals worked better than fixed targets because they adjust to each person's progress and keep them motivated.

2. Dietary goals, such as improving diet quality or reducing intake of ultra processed foods and sugar sweetened beverages, produced higher improvement rates than weight loss goals, highlighting the value of focusing on controllable behaviors.

3. Coping planning modules, interventions that help participants anticipate specific barriers to a target behavior and pre-plan concrete if-then strategies to overcome them, increased active minutes when goal setting alone did not.

4. Engagement frequency. Interventions with high weekly engagement had the strongest impact on both weight and HbA1c, suggesting that trial tools should support not only weekly goal cycles but also daily self-monitoring to sustain the behavioral awareness that maintains high engagement.

Across these goal-setting trials, retention to the primary endpoint was well above typical AOM trial retention (often 80–90% or higher), supporting the conclusion that high quality behavioral engagement design can meaningfully contribute to retention.

An important practical implication is that behavioral goal attainment should be tracked separately from weight outcomes.

From Uniform Support to Predictive, Data-Driven Engagement

Traditional retention strategies have tended to be uniform: everyone receives the same educational materials, the same schedule of contacts, and the same reminders. This approach does not reflect the heterogeneity in how people living with obesity experience treatment, side effects, and life circumstances over the course of a trial.

Digital tools and electronic patient-reported outcome (ePRO) platforms allow us to enhance patient engagement in a more data‑informed way. By combining ePRO metadata (completion rates, time‑of‑day patterns, response delays) with clinical data such as weight trajectories, visit history, and titration patterns, we can identify early signs of disengagement and tailor support to each participant. This information can trigger tiered engagement pathways, from automated reminders through to targeted site outreach and personalized counselling, before disengagement results in a missed visit or withdrawal.

Importantly, these enhanced engagement systems must be designed with attention to fairness and operational feasibility. They require standardized data streams, clear escalation protocols, and ongoing performance monitoring to avoid introducing bias or overwhelming sites with alerts. When implemented carefully, however, they shift retention work from reactive troubleshooting to proactive support, helping to keep patients engaged and in the trial.

What We Have Learned from Large-Scale Obesity Programs 

At Signant Health, we have supported more than 37 GLP-1 RA protocols across over 35 countries, involving approximately 17,500 participants and more than 600 research sites. This portfolio has allowed us to observe how engagement strategies and digital workflows translate into real-world retention and data quality.

Across AOM trials, average study visit attendance was 93.4%, markedly higher than adherence rates reported in published meta-analyses of weight loss interventions. Home-based visit compliance averaged 72% in studies that used visit scheduling modules and telehealth, roughly 7 percentage points higher than typical long term trial compliance benchmarks. These improvements are not attributable to any single feature; rather, they emerge from a combination of user-friendly ePRO design, clear visit schedules, proactive communication, and integration of support resources such as dietitians and telehealth.

We treat patient retention, data quality, and equity as designed outcomes. This means standardizing engagement packages that combine adaptive goal setting, flexible visit options, and structured site support, while allowing for regional adaptation.  It also demands integrating risk stratification and predictive analytics into routine operations, underpinned by standardized training, site calibration, and monitoring for subgroup disparities in engagement and outcomes.

At Signant Health, we promote patient engagement by combining standardized engagement packages with configurable local implementation. Our programs integrate patient education, adaptive goal‑setting, site support, user‑centered ePRO and visit‑schedule tools, telehealth options, and real‑time monitoring of ePRO and visit data to detect early signs of disengagement. When risk signals emerge, predefined pathways guide sites through targeted outreach and additional support, helping participants stay on treatment while preserving data quality and consistency across regions.

Looking Ahead: Retention as a Shared Responsibility 

Obesity trials sit at the intersection of high impact pharmacology, complex comorbidity management, and evolving regulatory expectations for long term safety, cardiometabolic outcomes, and mental health monitoring. Sustained participant engagement is the thread that connects these domains: without it, even the most promising therapy cannot be fully evaluated.

The evidence tells us that robust retention is achievable when we combine behavioral science, digital infrastructure, and thoughtful trial design. Financial incentives, structured self-monitoring, multicomponent support, adaptive goal-setting, and predictive analytics are not competing approaches; they are complementary components of a modern engagement strategy. The challenge is to move from theory to practice and to implement them systematically and effectively, so that high retention becomes the norm rather than the exception in obesity drug development.

About the authors.

Marcela Roy, MA, is Executive Director, Clinical Science & Medicine at Signant Health. She has been with Signant for over 15 years and has over 20 years of clinical and research experience. Her focus is Mood Disorders and Endpoint Reliability quality monitoring. She provides strategic direction in the organization, as well as team leadership and business development support. 

Lauren Crooks, MSc has comprehensive cross-functional experience within the life sciences and information technology sectors. At Signant, she combines this experience to provide scientific consultation and support to clients on the implementation of eCOA to optimize patient care and outcomes in clinical trials. She has supported eCOA projects across multiple therapeutic areas, including dermatology and neurology, with a current focus on respiratory diseases. 

Dr. Graham C Ellis, MD, is Clinical Vice President at Signant Health. A specialist physician with more than 25 years of experience in diabetes, endocrinology, and metabolic disease, he has served as Principal Investigator on more than 150 international clinical trials. Dr. Ellis previously served as Executive Director of Medical Science and Strategy at PPD, the clinical research business of Thermo Fisher Scientific, and is a founding member of the Centre for Diabetes and Endocrinology (CDE).

Elias Ketiar, MD, MRCP serves as the Clinical Vice President, Science & Medicine, at Signant Health. Dr. Ketiar draws on his wealth of more than 20 years of academic and clinical experience to advise on clinical trial design, execution, and governance. He has extensive experience in General Internal Medicine and Cardiology and is a Member of Royal College of Physicians (London), UK. Dr Ketiar has been engaged in academic research and was involved in a pioneering project investigating genetic causes of congenital heart disease, which culminated in a Medical Doctorate with St George’s University of London, UK. He also has peer reviewed papers published. He has always been involved in all phases of clinical development and interested in global clinical trial solutions.