Abstract:
Background: Weight Management Medications (WMMs) demonstrate significant benefits including weight loss and improvement in cardiovascular risk factors (blood pressure, lipid profile, HbA1c levels, inflammation), while behaviorally reducing food cravings, "food noise", and addictive behavior. However, recent evidence indicates a clinically meaningful rebound effect after stopping WMMs, including weight regain, return of cardiometabolic risk factors, and relapse into unhealthy behaviors. The STEP 1 extension study showed that one year after cessation of GLP-1 use, patients had regained two-thirds of the weight previously lost (despite receiving lifestyle interventions during initial clinical trial), and changes in cardiometabolic variables returned towards baseline. Among patients using GLP-1 agonists for the first time, 30% discontinued within 3 months and 50% discontinued within a year. Patients living with obesity are at high risk of dropping out of WMM trials due to gastrointestinal side effects (nausea, vomiting, and diarrhea), early dropout during dose escalation, delayed perceived benefit, preference for oral medications, in-clinic visit demands, and mismatch between expectations and reality.
Objective: To present evidence-based strategies for improving patient engagement and reducing attrition in weight management medication clinical trials.
Methods: This analysis draws from: (1) A systematic review by Pirotta et al. (2019) examining weight loss interventions across 57 studies with over 7,500 participants to identify effects of intervention strategies on attrition, (2) Signant Health's experience across 39 obesity Phase 2 and 3 studies implementing electronic patient-reported outcome (ePRO) collection and digital patient engagement solutions involving 8,836 patients in 35 countries at 579 sites, and (3) additional research including gamification studies (Forman et al., 2023) with 228 men and dietitian support programs (Delahanty et al., 2016) with 4,410 participants across 15 countries in Phase 3 trials.
Results: Systematic review findings (Pirotta et al., 2019) demonstrated:
- Financial incentives reduced risk of attrition by up to 43%
- Self-monitoring reduced risk of attrition by 41%
- Multicomponent interventions (nutrition, activity, psychological help) reduced attrition by 33%
Signant Health's case study data showed:
- 93.4% average study visit total compliance across weight management trials, exceeding mean study visit adherence rate of 64%
- 72% average total compliance in home-based compliance across patient engagement studies (obesity, neurofibromatosis, sickle cell disease) utilizing visit schedule module and telehealth, representing ~7% greater compliance compared to the average of 65% across long-term trials
Additional program outcomes:
- Dietitian support programs (Delahanty et al., 2016): 82% median 1-year retention
- Behavioral screening reduced dropout by 29% (US cohort)
- Attending five monthly dietitian support calls reduced dropout rates by 32%
Conclusions: Evidence supports that engagement strategies can significantly improve retention in weight management trials. The clinical trial community has an opportunity to understand and proactively mitigate the effects of WMM discontinuation through collaborative strategies including educating trial staff and patients about physical, behavioral, and emotional impacts of WMMs, training site staff to recognize and address obesity bias, implementing patient-centric digital solutions, and offering ongoing support to ensure patients feel informed and well-supported.
Clinical Implications: Given that there is no evidence that patients living with obesity will remain engaged for trial duration or will be able to access WMMs following the study, implementing patient engagement strategies is critical for obesity trials.
