Exenatide Improves Cardiovascular Risk Factors in Absence of Clinically Significant Weight Loss in Overweight and Obese Women without Diabetes

Objective : Glucagon-like peptide-1 (GLP-1) receptor agonists, initially used as powerful agents for glycemic control and cardiovascular benefit in individuals with diabetes, have emerged as weight loss therapies for those with obesity and without diabetes. Benefits beyond weight loss for this new population are not fully known. Prior studies suggest that the GLP-1 receptor agonist exenatide improves cardiovascular risk factors, including blood pressure and lipid profile, in overweight and obese women without diabetes who achieve clinically significant weight loss. In this study, we investigate whether these benefits are seen even in the absence of clinically significant weight loss.

Methods: As part of a larger study of overweight and obese women without diabetes, 69 women (age 43.0±11.9 years, BMI 36.4±5.4 kg/m²) were treated with exenatide 10 mcg twice daily. Participants were classified by weight loss response by 12 weeks: those without clinically significant weight loss ( < 5% body weight) were low responders (LR, n=38, average weight change -2.3%; range +2.6% to -4.9%); high responders lost ≥ 5% body weight (HR, n=31, -7.1%; -5.1% to -15.1%). We measured 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) at randomization and 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: At 12 weeks, hs-CRP levels did not change in either weight loss HR (4.6±4.1 to 4.2±3.8 mg/L; p=0.51) or LR (4.2±3.5 to 4.9±4.2 mg/L; p=0.06). In HR, exenatide 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). In LR, exenatide also significantly reduced SBP (-4.7 mmHg; p< 0.05), TC (-11.3 mg/dL; p< 0.001), and LDL (-4.9 mg/dL; p< 0.02), but not TG (+0.04 mg/dL; p=0.83).

Discussion/Conclusion: After 12 weeks of treatment with exenatide, the subset of overweight and obese women without diabetes who demonstrated early clinically significant weight loss achieved significant reductions in blood pressure and improved lipid profile. Notably, the subset of participants who did not achieve at least 5% weight loss also had significantly reduced SBP, TC, and LDL levels. This suggests that some cardioprotective benefits of GLP-1 receptor agonists emerge regardless of weight loss; these agents could be more widely considered for cardiovascular benefit among those without diabetes.