Long-Acting Lipid-Lowering Injectables and Behavioral Moral Hazard: A Systematic Review of Adherence, Lifestyle Measurement, and Structural Evidence Gaps

Background/Objectives: Long-acting lipid-lowering injectable therapies, including PCSK9 monoclonal antibodies, inclisiran, and selected glucagon-like peptide-1 receptor agonists, represent a structural innovation in chronic disease management. By reducing dosing frequency and embedding pharmacologic persistence within healthcare delivery systems, these therapies address persistent challenges of long-term statin non-adherence. However, from a health economics perspective, such innovations may also alter incentive structures related to preventive behaviors. This study examines whether outcome measurement in the long-acting injectable literature reflects shifts in the balance between pharmacologic adherence and lifestyle-related prevention. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Eligible studies included adult populations receiving PCSK9 monoclonal antibodies, inclisiran, or GLP-1 receptor agonists that reported pharmacologic adherence or persistence and/or lifestyle-related measures. Studies were categorized by therapy class and design. The prevalence of adherence and lifestyle outcome measurement was calculated, and a descriptive Measurement Asymmetry Index was defined as the difference between adherence measurement prevalence and lifestyle measurement prevalence. Results: Four studies met the inclusion criteria, comprising randomized controlled trials. Pharmacologic adherence or persistence was measured in all included studies (100%), whereas lifestyle-related outcomes were assessed in only one study (25%), limited to a GLP-1 receptor agonist trial. No study explicitly evaluated behavioral substitution, risk compensation, or changes in patient responsibility. The Measurement Asymmetry Index was 75 percentage points, indicating a pronounced imbalance between pharmacologic and behavioral outcome domains. Conclusions: The findings do not provide evidence of behavioral moral hazard at the individual level but reveal a structural asymmetry in how prevention is assessed within the injectable therapy evidence base. This pattern may reflect an emphasis on drug-attributable and measurable outcomes, with comparatively limited attention to lifestyle engagement. As long-acting therapies become more integrated into chronic disease management, incorporating standardized lifestyle metrics into cardiovascular research may be necessary to support a more balanced framework of preventive responsibility.