Reducing Dropout in Anti-obesity Medication Trials

Participant dropout rates of 15-30% in anti-obesity medication trials directly threaten the statistical power and scientific validity of evidence submitted for regulatory approval. Three evidence-based intervention categories reduce attrition risk by 32-43% and are available for implementation now.

What this whitepaper examines:

• Attrition rates of 15-30% have been reported across major Phase 3 anti-obesity programs, including STEP (semaglutide) and SURMOUNT (tirzepatide), with gastrointestinal adverse events, perceived lack of efficacy, and logistical burden identified as primary drivers of dropout.

• A systematic review by Pirotta et al. (2019) across 57 studies and 7,500 participants found financial incentives reduced attrition risk by 43%, self-monitoring interventions by 41%, and multicomponent support programs by 33%.

• Dietitian support programs achieved an 82% median one-year retention rate across 4,410 participants in 15 countries, with structured teleconference contact reducing dropout rates by 32% (Delahanty et al., 2016).

• Behavioral goal setting, specifically dietary goals over weight targets, improved goal attainment by 71% versus 39% for weight-loss goals, with adaptive percentile-based approaches consistently outperforming static targets (Crooks et al., 2025, ECO poster presentation).

• Signant Health's implementation across 37 GLP-1 protocols in more than 35 countries, supporting 17,500 participants across 640 research sites, achieved 93.4% average study visit attendance and 72% home-based visit adherence.

• The full whitepaper details a predictive analytics framework for identifying dropout risk before discontinuation occurs, including ePRO metadata analysis, engagement scoring thresholds, and tiered site intervention protocols not covered on this page.

Why Participant Dropout in AOM Trials Is a Regulatory Problem Now

When a participant living with obesity discontinues a multi-year trial, the consequences are not limited to missing data. Dropout reduces statistical power, introduces bias into efficacy and safety analyses, and creates intercurrent events that must be addressed in study design and interpretation under ICH E9(R1). If discontinuation is not managed as a pre-specified intercurrent event, submissions risk rejection.

The urgency is active now. The FDA's 2025 guidance on developing drugs for the treatment of obesity explicitly recommends that at least one Phase 3 trial integrate a standardized, scalable lifestyle-modification program alongside pharmacotherapy. That expectation applies to trials in design today. Sponsors who treat engagement as an operational afterthought, rather than a designed trial element, face both a retention problem and a regulatory one.

People living with obesity who enroll in multi-year trials carry a burden that extends well beyond treatment side effects: the daily reality of managing a chronic condition, navigating injections, attending frequent visits, and persisting through months of uncertain response. Engagement strategies that ignore this reality do not work.

What the Evidence Shows and What the Whitepaper Provides

Many sponsors have historically relied on blanket retention approaches: uniform reminders, standardized site contacts, and generic patient education. These approaches are defensible given the complexity of customizing support at scale. But the systematic evidence now available gives sponsors no reason to continue with them.

The whitepaper authored by Signant Health's Science and Medicine team, drawing on Signant's clinical trial database of 39 obesity Phase 2 and Phase 3 studies involving 8,836 participants, presents a four-layer retention framework: evidence-based engagement design, goal-setting implementation parameters, predictive dropout analytics, and bias-aware standardization across demographic subgroups.

Each layer is grounded in peer-reviewed sources, including Pirotta et al. (2019), Delahanty et al. (2016), and a Signant-authored goal-setting systematic review submitted to the European Congress on Obesity in May 2026. Sponsors designing or amending GLP-1 or incretin-based AOM programs will find the specific implementation criteria, engagement frequency thresholds, and escalation protocols not summarized here.

"The question is no longer whether we can solve this problem. The evidence demonstrates that we have both the understanding and the tools to transform participant retention in obesity trials. The imperative now is to implement these proven solutions rapidly and systematically across the industry." — Dawie Wessels, MD, Chief Medical Officer, Signant Health 

AUTHOR BIO 

Name: Marcela Roy 
Title and Credentials: MA, Executive Director, Science and Medicine, Signant Health 
Bio: Marcela Roy 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.  

Want to discuss participant retention strategy for your next GLP-1 or anti-obesity medication program? Speak to a clinical engagement expert.