Pharmacy Practice
The persistence gap in incretin-based pharmacotherapy for obesity: A Scoping review of clinical efficacy versus real-world effectiveness
By Kush Amin.
Abstract
Background
Incretin-based therapies (semaglutide and tirzepatide) represent a new pharmacological benchmark for chronic weight management. Despite achieving sustained weight reductions exceeding 14% in Phase 3 randomized controlled trials (RCTs), their population-level impact is constrained by real- world medication persistence failures. Insurance-driven access barriers and sub-therapeutic dosing practices may undermine the clinical gains demonstrated in controlled settings.
Objective
To systematically map the Persistence Gap between RCT completion rates and real-world adherence, characterize temporal trends in persistence across the 2021-2025 period, identify structural drivers of discontinuation, and assess the health consequences of treatment cessation.
Methods
Following PRISMA-ScR guidelines, a structured PubMed/MEDLINE search was conducted on December 31, 2025, covering January 1, 2021 through December 31, 2025. The protocol was prospectively registered on OSF (February 4, 2026). Ten core evidence sources were included following two-stage screening of 152 records: four RCT post-hoc analyses, three real-world electronic health record/claims studies, one pharmacy benefit manager longitudinal report, one observational cohort study, and one government policy document.