Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect?

Sep 28, 2018Current cardiology reports

Do Drugs That Activate Glucagon-Like Peptide-1 Receptors Lower Heart Risks in Type 2 Diabetes as a Group?

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Once-daily liraglutide and once-weekly semaglutide showed significant superiority in reducing major adverse cardiovascular events (MACE) in adults with type 2 diabetes mellitus (T2DM).

GLP-1 receptor agonists (GLP-1 RAs) improve glycemic control and may offer cardiovascular protection in adults with T2DM.
Statistically significant non-inferiority (p < 0.001) was observed in cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs to standard antidiabetic therapies.
Liraglutide and semaglutide demonstrated significant reductions in 3-point composite MACE with p-values of 0.01 and 0.02, respectively.
Once-weekly exenatide showed a non-significant favorable trend (p = 0.06) for cardiovascular superiority, potentially affected by trial mishaps.
Lixisenatide was neutral (p = 0.81) in MACE reduction, likely due to ineffective once-daily dosing.
Structural differences among GLP-1 mimetics may influence their effectiveness in A1C reduction and cardiovascular protection.

AI simplified

PURPOSE OF REVIEW: Mimetics and analogs that extend the half-life of native glucagon-like peptide-1 (GLP-1), i.e., glucagon-like peptide-1 receptor agonists (GLP-1 RAs), at therapeutic doses, are indicated as adjuncts to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). In patients with T2DM, GLP-1 RAs not only affect improvements in impaired beta cell and alpha cell function, suppress appetite, and induce weight loss but also possess multiple cardiovascular protective properties that potentially have a beneficial impact on atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality.

RECENT FINDINGS: Required to demonstrate CV safety, compared to standard-of-care antidiabetic therapies, GLP-1 RAs have revealed statistically significant non-inferiority (p < 0.001), among CV outcome trials (CVOTs) thus far completed. Once-daily liraglutide and once-weekly semaglutide demonstrated significant superiority (p = 0.01 and p = 0.02, respectively), reducing 3-point composite major adverse cardiovascular events (MACE) in extreme risk secondary prevention adults with T2DM. Once-weekly exenatide demonstrated only a non-significant (p = 0.06) favorable trend for CV superiority, possibly due to in-trial mishaps, including placebo drop-ins with other CV protective medications. The short half-life lixisenatide was neutral (p = 0.81) in reducing MACE, most likely due to ineffective once-daily dosing. Structural differences among GLP-1 mimetics and analogs may explain potency differences in both A1C reduction and weight loss that may parallel important cardiovascular protective properties of the GLP-1 RA class. Significant superiority in reducing 3-point composite MACE in adults with T2DM with GLP-1 RAs has been limited to liraglutide and semaglutide. Careful attention to within-trial drop-in of cardioprotective antidiabetic agents assuring equipoise between placebo and investigational product groups might demonstrate significant MACE risk reduction with once-weekly exenatide. Maintenance of 24-h circulating levels, by an alternative administration method, may resurrect lixisenatide as a cardioprotective agent. Before a GLP-1 RA bioequivalence "class effect" claim for composite MACE risk reduction superiority can be fully discussed, we are obliged to wait for the pending results of CVOTs with other GLP-1 RAs, particularly albiglutide and dulaglutide, where steric hindrance may potentially inhibit full mimicry of pharmacologic GLP-1.

Full Text

Full text is available at the source.

View full text (HTML) ↗View full text (PDF) ↗

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect?

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief