GLP-1 use linked to lower mortality in adults with obesity and elevated CRP

Clinical takeaway: For adults with obesity and elevated C-reactive protein, these findings may inform discussions of potential long-term GLP-1 benefits.

Obesity often accompanies low-grade inflammation, which contributes to cardiovascular risk. A new study examined whether GLP-1 receptor agonist use was associated with better long-term outcomes in adults with obesity and elevated C-reactive protein (CRP), a blood marker of inflammation.

Researchers used electronic health records to compare 50,009 GLP-1 users with 50,009 matched adults receiving metformin, orlistat, or phentermine without GLP-1 exposure. All had a BMI of at least 30 and CRP levels of 3–10 mg/L. Follow-up extended up to ten years.

GLP-1 use was associated with a 21% lower hazard of death from any cause, acute myocardial infarction, or ischemic stroke combined. The association was driven mainly by a 39% lower mortality hazard. Estimated ten-year survival was 80.3% versus 73.8%.

Ischemic stroke, arrhythmias, and heart failure with reduced ejection fraction were modestly lower. MIs and new diagnoses of heart failure with preserved ejection fraction did not differ significantly.

The study could not determine whether reduced inflammation, weight loss, or other changes explained the associations, or whether higher CRP predicted greater benefit.

“These hypothesis-generating findings support prospective studies incorporating CRP and weight trajectories to evaluate mediation and determine whether inflammatory burden identifies patients who derive greater absolute benefit from GLP-1 RA therapy,” the authors concluded.

Source: Shah S, et al. (2026 Sept 21) Am J Cardiol. GLP-1 Analogues and Long-Term Outcomes in Adults With Obesity and Elevated CRP: A Real-World Matched Cohort Study