Real-World Evidence for Existing Anti-Obesity Therapies-The Realities of Treatment Adherence, Tolerability, Access...

Obesity is associated with substantial cardiometabolic and psychosocial morbidity. Although randomized controlled trials demonstrate the efficacy of anti-obesity therapies, outcomes in real-world practice may be attenuated due to limited access, tolerability, adherence and insufficient long-term support.

This narrative review aimed to synthesize real-world evidence on adherence, tolerability, access and patient satisfaction across lifestyle programmes, pharmacotherapy, metabolic bariatric surgery (MBS) and endoscopic procedures, with emphasis on incretin-based medications.

PubMed/MEDLINE search was conducted through July 2026. Studies reporting real-world treatment effectiveness, adherence, persistence, discontinuation, tolerability, access or patient satisfaction in adults or adolescents with overweight or obesity were included. Randomized trials and reviews were used to contextualize real-world findings.

Intensive lifestyle interventions generally achieve approximately 5% weight loss, but attrition and weight regain after programme completion are common. Incretin-based therapies, including semaglutide and tirzepatide, produce substantial weight loss in trials but real-world effectiveness is relatively smaller because of non-initiation, incomplete dose escalation, gastrointestinal adverse effects, treatment interruptions, and financial or insurance barriers. Older medications demonstrate poor persistence, largely related to neurologic, psychiatric or gastrointestinal intolerance, despite lower costs for some agents. MBS provides the greatest and most durable weight loss but remains substantially underused, with racial, socioeconomic and insurance disparities. Endoscopic sleeve gastroplasty offers moderate, durable weight loss with low serious adverse event rates, whereas intragastric balloons are more limited by intolerance, reintervention and weight regain after removal.

Real-world effectiveness is determined not only by biological efficacy but also by treatment tolerability, adherence, access and sustained support. Proactive adverse effect management, individualized behavioural support, streamlined referral pathways and policies that improve affordability and equitable access are essential to narrowing the trial-to-practice gap.