From the Guidelines
Semaglutide appears to have the most cardiovascular benefit among GLP-1 receptor agonists, as evidenced by its superior performance in clinical trials compared to other GLP-1 analogs 1. Semaglutide (brand name Ozempic) has demonstrated superior cardiovascular outcomes in clinical trials compared to other GLP-1 analogs. The typical starting dose is 0.25 mg once weekly, increased gradually to 1 mg weekly for maximum effect. To implement this:
- Start with 0.25 mg subcutaneous injection once weekly for 4 weeks
- Increase to 0.5 mg weekly for 4 weeks
- Then increase to 1 mg weekly as the maintenance dose Semaglutide's enhanced cardiovascular benefit is likely due to its longer half-life and greater potency in activating the GLP-1 receptor. This leads to more consistent blood glucose control, greater weight loss, and improved lipid profiles. Additionally, semaglutide may have direct beneficial effects on the cardiovascular system, including reducing inflammation and improving endothelial function. While other GLP-1 analogs like liraglutide and dulaglutide also show cardiovascular benefits, current evidence suggests semaglutide offers the most pronounced risk reduction for major adverse cardiovascular events in patients with type 2 diabetes, as supported by the most recent study 1.
The most recent study 1 provides the strongest evidence for semaglutide's cardiovascular benefits, and its findings are consistent with those of previous studies 1. The study's results demonstrate that semaglutide reduces the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal MI, and nonfatal stroke, in patients with type 2 diabetes. The dosing regimen for semaglutide is well-established, and its safety profile is generally favorable, with the most common adverse events being gastrointestinal in nature 1.
Overall, the evidence supports the use of semaglutide as the preferred GLP-1 receptor agonist for patients with type 2 diabetes who are at high risk for cardiovascular events, due to its superior cardiovascular benefits and favorable safety profile 1.
From the FDA Drug Label
OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1) TRULICITY® is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated (1): To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors
The GLP-1 analogs semaglutide and dulaglutide have been shown to have cardiovascular benefits.
- Semaglutide is indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 2.
- Dulaglutide is indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors 3. However, the provided information does not allow for a direct comparison of the magnitude of cardiovascular benefit between semaglutide and dulaglutide.
From the Research
GLP-1 Analogues with Cardiovascular Benefits
The following GLP-1 analogues have demonstrated cardiovascular benefits:
- Liraglutide: has been shown to reduce major adverse cardiovascular events (MACE) and progression of chronic kidney disease (CKD) 4
- Semaglutide: has been shown to reduce MACE and renal events, with a significant reduction in HbA1c levels 4, 5
- Dulaglutide: has been shown to reduce MACE, with a significant reduction in HbA1c levels 6
Comparison of GLP-1 Analogues
A comparison of the different GLP-1 analogues shows that:
- Semaglutide has a robust reduction in HbA1c levels, up to 1.5-1.8% 5
- Liraglutide, dulaglutide, and subcutaneous semaglutide have demonstrated significantly lower MACE versus placebo 6
- Oral semaglutide has been shown to improve body weight, blood pressure, HbA1c, LDL-C, non-HDL-C, and UACR in type 2 diabetic obese patients, especially in those who had not previously used GLP-1 analogues 4
Clinical Evidence and Best Practice
Clinical evidence and best practice guidelines recommend the use of GLP-1 receptor agonists, including liraglutide, dulaglutide, and semaglutide, for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes 6, 7
- These agents have been shown to pose no additional cardiovascular risk compared with placebo, and have been approved for the indication of reducing MACE 6
- GLP-1 receptor agonists are recommended as a therapeutic option in various settings, including in patients at high risk of or with established atherosclerotic cardiovascular disease, regardless of HbA1c levels 8