Effects of glucagon-like peptide-1 (GLP-1) receptor agonists on cardiovascular risk factors: a narrative review of head-to-head comparisons

Cardiovascular (CV) disease is the leading cause of death and morbidity in patients with type 2 diabetes. Five CV risk factors (blood pressure, resting heart rate [HR], body weight, cholesterol levels and blood glucose) are monitored routinely as safety and efficacy endpoints in randomised clinical trials for diabetes therapies. To determine if different glucagon-like peptide-1 receptor agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16 head-to-head trials directly comparing GLP-1RAs that included at least one of the five factors. Few trials reported statistical differences between GLP-1RAs in terms of systolic blood pressure (SBP), body weight and total cholesterol. Liraglutide increased heart rate versus its comparators in three separate trials. All GLP-1RAs reduced glycated haemoglobin (HbA1c), but exenatide twice daily and lixisenatide had statistically smaller effects compared with other GLP-1RAs. These descriptive data indicate that individual GLP-1RAs affect CV risk factors differently, potentially due to their individual pharmacokinetics and/or size. Short-acting GLP-1RAs appeared to result in smaller changes in SBP and total cholesterol compared with continuous-acting treatments, while large GLP-1RAs had a reduced effect on body weight compared with small GLP-1RAs. For glycaemic control, short-acting GLP-1RAs had a greater impact on post-prandial glucose levels versus continuous-acting GLP-1RAs, but for fasting plasma glucose levels and HbA1c, continuous-acting treatments had the greater effect. No differentiating trends were obvious in HR data. These diverse actions of GLP-1RAs on CV risk factors should aid individualised patient treatment.