Journal of managed care & specialty pharmacyAug 30, 2018

Heart health and cost impacts of once-weekly GLP-1 receptor agonist treatments

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

A phase 3 trial of exenatide extended release found no significant difference in reducing major adverse cardiac events (MACE) compared to placebo in patients with type 2 diabetes mellitus (T2DM).

Type 2 diabetes mellitus is linked to a higher risk of atherosclerotic cardiovascular disease.
Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have beneficial effects on cardiovascular risk factors.
Liraglutide has shown superior clinical outcomes in reducing cardiovascular events.
Semaglutide significantly reduced the risks of MACE and non-fatal stroke compared to placebo in a high-risk population.
Ongoing research (REWIND trial) is assessing the impact of dulaglutide on MACE.

Simplified

UNLABELLED: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM.

DISCLOSURES: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.

Funding

Competing interests

This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.

PubMed

Heart health and cost impacts of once-weekly GLP-1 receptor agonist treatments

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