Key result
GLP-1 RAs linked to ~20% lower risk of death, MI, and stroke vs active controls.
Why the study?
Obesity is frequently accompanied by low-grade systemic inflammation and increased cardiovascular risk, but the association of GLP-1 RA exposure with long-term outcomes in adults with obesity and elevated CRP was unclear.
Does GLP-1 RA exposure reduce the composite outcome of mortality and cardiovascular events in adults with obesity and elevated CRP (3 to 10 mg/L) compared to active alternatives?
Cohort (n=100,018)
Yes
Does GLP-1 RA exposure reduce the composite outcome of mortality and cardiovascular events in adults with obesity and elevated CRP (3 to 10 mg/L) compared to active alternatives?
Hazard Ratio: 0.799 (95% CI 0.772–0.825)
p-value: p=< 0.001
In a real-world cohort of adults with obesity and systemic inflammation (CRP 3-10 mg/L), GLP-1 RA use was associated with significantly lower long-term risk of adverse cardiovascular events and all-cause mortality compared to other weight-management therapies.
GLP-1 RA exposure was associated with lower composite risk in obese adults with elevated CRP; hypothesis-generating and should not yet change practice.
Obesity is frequently accompanied by low-grade systemic inflammation and increased cardiovascular risk. We evaluated whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) exposure was associated with improved long-term outcomes among adults with obesity and C-reactive protein (CRP) levels of 3 to 10 mg/L. Using the TriNetX Global Collaborative Network, adults with body mass index ≥30 kg/m² who received a GLP-1 RA were compared with an active-comparator cohort receiving metformin, orlistat, or phentermine without GLP-1 RA exposure. Following 1:1 propensity-score matching, 50,009 patients were included in each cohort and followed for up to 3,650 days. GLP-1 RA exposure was associated with a lower hazard of the primary composite outcome of all-cause mortality, acute myocardial infarction, and ischemic stroke (hazard ratio [HR] 0.799, 95% confidence interval [CI] 0.772-0.825; p < 0.001), driven primarily by lower all-cause mortality (HR 0.608, 95% CI 0.578-0.640; p < 0.001). Ischemic stroke, arrhythmias, and heart failure with reduced ejection fraction were modestly lower, whereas acute myocardial infarction and incident heart failure with preserved ejection fraction did not differ significantly between cohorts. In conclusion, GLP-1 RA exposure was associated with lower long-term composite clinical events among adults with obesity and CRP levels of 3 to 10 mg/L, predominantly reflecting lower mortality; prospective studies incorporating longitudinal weight and CRP measurements are needed to evaluate potential mediating mechanisms.
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Shah et al. (2026) conducted a cohort in Obesity and elevated C-reactive protein (n=100,018). Glucagon-like peptide-1 receptor agonist (GLP-1 RA) vs. Active-comparator cohort receiving metformin, orlistat, or phentermine was evaluated on Composite of all-cause mortality, acute myocardial infarction, and ischemic stroke (HR 0.799, 95% CI 0.772-0.825, p=< 0.001). GLP-1 RA exposure was associated with a lower risk of all-cause mortality, myocardial infarction, and ischemic stroke compared to active controls (HR 0.799; 95% CI 0.772-0.825; p < 0.001).
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