Effect of Exenatide Versus Hypocaloric Diet on High-sensitivity C-reactive Protein and Other Cardiovascular Risk Factors in Overweight and Obese Women without Diabetes

Objective : Obesity is associated with poor cardiovascular outcomes independent of comorbid diabetes; inflammation is a proposed link. In overweight and obese individuals with diabetes, glucagon-like peptide 1 (GLP-1) receptor agonists improve markers of inflammation and cardiovascular risk. Whether this effect persists in individuals without diabetes is not known. We evaluated the effect of exenatide, a GLP-1 receptor agonist, on inflammation and cardiovascular risk factors compared to hypocaloric diet and placebo injections in overweight and obese women without diabetes who demonstrated early clinically significant weight loss.

Methods: 108 women were randomized to treatment with either exenatide (E, 10 mcg twice daily) or hypocaloric diet plus placebo injections (D/PBO). High responders (age 44.1±12.2 years, BMI 36.2±5.7 kg/m²) lost ≥ 5% body weight by 12 weeks. In a subset of high responders (E: n=31, D/PBO: n=17), high-sensitivity C-reactive protein (hs-CRP), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides (TG) were measured at baseline and after 12 weeks of treatment. Our primary outcome was change in hs-CRP. Secondary outcomes were change in SBP, DBP, and lipid parameters. Data were analyzed with Student’s T-test; p-values < 0.05 were considered significant.

Results: There was no significant change in hs-CRP by 12 weeks in either E (4.6±4.1 to 4.2±3.8 mg/L, p=0.51) or D/PBO (4.7±3.9 to 4.4±5.0 mg/L, p=0.67) high responders. However, at 12 weeks, E showed significantly reduced SBP (-6.3 mmHg; p< 0.02), TC (-20.3 mg/dL; p< 0.0001), LDL (-9.9 mg/dL; p< .02), and TG (-19.3 mg/dL; p< 0.05). D/PBO had significantly reduced SBP (-10.0 mmHg; p< 0.02), DBP (-6.1 mmHg; p< 0.01), TC (-18.9 mg/dL; p< 0.03) and TG (-26.9 mg/dL; p< 0.006) but did not significantly change LDL (-6.8 mg/dL; p=0.59).

Discussion/Conclusion: Many studies report that weight loss is associated with decreased hs-CRP, though time course and degree of weight loss varies. Our study population of overweight and obese women without diabetes had well-controlled blood pressure and lipid profiles at baseline, yet still benefited from weight loss ≥ 5%, with significant improvement in cardiovascular risk factors including SBP, TC, TG, and LDL. In contrast, this clinically significant weight loss did not lower serum hs-CRP. To detect an anti-inflammatory benefit of GLP-1 agonists in this population, future studies might require increased time to measurement of hs-CRP or higher degree of weight loss.