Analysis and Characterization of Variations in Conceptual and Operational Definitions for GLP-1 Agonist Treatment Eligibility for Weight Management

Author(s)

Jared H. Kamauu, BFA1, Michael Buck, PhD2, Amanda Shields, BA3, Craig G Parker, MD, MS2, Aaron Kamauu, MD, MS, MPH2.
1Knowledge Engineer, Navidence, Salt Lake City, UT, USA, 2Navidence, Salt Lake City, UT, USA, 3Navidence, Chapel Hill, NC, USA.
OBJECTIVES: Complex clinical concepts are often important indications for clinical research. Real-world research may include complex clinical concepts to define a cohort indication for treatment (e.g., inclusion/exclusion criteria), outcome measures, or other study elements. However, often there is not clear agreement on conceptual definitions, nor operational definitions. We demonstrate significant variations in conceptual and operational definitions from reputable sources for people indicated for glucagon-like peptide-1 (GLP-1) agonist treatment for weight management.
METHODS: We conducted a review of relevant literature, clinical guidelines (e.g., EMA, NHS/NICE), and clinical trials regarding GLP-1 agonist treatment for weight management. Details on qualifying characteristics were extracted, tabulated and analyzed, including requirements on age, weight category, and if a comorbidity is required (how many, and which ones). In addition, where published, operational definitions were assessed.
RESULTS: 14 sources were identified and assessed, all indicating GLP-1 agonist treatment for adults. 12 sources included “overweight” persons: 3 as BMI range of 25.0-29.9 kg/m2, and 9 narrow the definition of “overweight” to 27.0-29.9 kg/m2 (or regionally-appropriate equivalents). 13 sources included “obese” persons: 11 as ≥30 kg/m2, and 4 narrow “obesity” categories (i.e., 30-34.9, ≥35, 35-39.9, ≥40), not mutually exclusive. 12 sources had an operational definition of also requiring ≥1 qualifying comorbidity and 1 had definitions of ≥3 and ≥4. Across those 13 sources, 20 distinct comorbidities were indicated, with hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease being the most common. Several comorbidities had multiple different operational definitions: diagnosis vs. treatment patterns vs. specific lab or vital sign measurements.
CONCLUSIONS: While GLP-1 agonist treatments are common for weight management, understanding these variations in conceptual and operational definitions is essential for real-world research, as small differences in definition can have a large impact on study results.

Conference/Value in Health Info

2025-11, ISPOR Europe 2025, Glasgow, Scotland

Value in Health, Volume 28, Issue S2

Code

MSR27

Topic

Methodological & Statistical Research, Real World Data & Information Systems

Topic Subcategory

Confounding, Selection Bias Correction, Causal Inference, Missing Data

Disease

Diabetes/Endocrine/Metabolic Disorders (including obesity)

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