GLP-1-based therapy and ICD-10-documented heart failure or respiratory failure events in non-diabetic adults with rheumatoid arthritis and obesity: a TriNetX federated cohort study.
This retrospective federated cohort study used the TriNetX US Collaborative Network to examine whether GLP-1-based therapy (semaglutide or tirzepatide) was associated with lower rates of ICD-10-documented heart failure (HF) or respiratory failure (RF) in non-diabetic adults with rheumatoid arthritis (RA) and obesity (BMI ≥30 kg/m²). Patients were required to have baseline disease-modifying antirheumatic drug (DMARD) use, and those with diabetes or overlapping systemic autoimmune diseases were excluded. After propensity score matching on 68 covariates (1:1), 3,483 patients remained per cohort. The study found that GLP-1-based therapy was associated with a substantially lower hazard of first post-landmark composite HF or RF events during days 91–365. In absolute terms, the primary composite occurred in 0.7% of GLP-1 users versus 1.8% of never-users, corresponding to roughly one fewer event per 100 patients. Heart failure and respiratory failure analyzed separately showed directionally consistent lower hazards, though individual event counts were small. The authors acknowledge that the findings are hypothesis-generating only, are limited by the retrospective, administrative-data design and potential residual confounding, and require prospective validation before informing clinical practice.
Why this grade: While conducted in humans with propensity score matching, the study is retrospective and relies on ICD-10 codes in an administrative database, with small absolute event counts and acknowledged potential for residual confounding, precluding strong causal inference.
Introduction/objectives Glucagon-like peptide-1 (GLP-1)-based therapies have emerged as a major advance in cardiometabolic care; however, no prospective outcomes data exist for these agents in non-diabetic adults with rheumatoid arthritis (RA) and obesity. We examined whether GLP-1-based therapy was associated with first post-landmark ICD-10-documented heart failure (HF) or respiratory failure (RF) events. Methods We conducted a retrospective cohort study in the TriNetX US Collaborative Network. Adults with RA, body mass index ≥ 30 kg/m 2 , and baseline-year disease-modifying antirheumatic drug (DMARD) therapy were included; patients with diabetes and overlapping systemic autoimmune diseases were excluded. Exposure was semaglutide or tirzepatide documented within 0-90 days after the index BMI, and comparators were strict never-users. Cohorts were propensity score-matched 1:1 on 68 covariates. The primary endpoint was the first post-landmark ICD-10-documented HF or RF during days 91-365 among patients without pre-index documentation of the corresponding endpoint. Results After matching, 3483 patients remained per cohort, with all standardized mean differences Conclusions GLP-1-based therapy was associated with substantially lower hazards of first post-landmark ICD-10-documented HF or RF events. These observations, while compelling, are hypothesis-generating and require prospective validation before informing clinical use. Key Points • In a propensity score-matched TriNetX cohort of non-diabetic adults with rheumatoid arthritis and obesity, GLP-1-based therapy was associated with a lower hazard of first post-landmark ICD-10-documented heart failure or respiratory failure events. • In absolute terms, the primary composite occurred in 0.7% of GLP-1 users and 1.8% of never-users during days 91-365, corresponding to approximately one fewer event per 100 patients. • Heart failure and respiratory failure, analyzed separately, showed directionally consistent lower hazards, although event counts were small. • The findings provide preliminary RA-specific evidence for a prospective study, but they should not be used to guide treatment decisions.
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