Journal of clinical pharmacy and therapeuticsSep 10, 2020

Heart safety of once-weekly GLP-1 treatments in people with type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 28, 2026

Abstract

Three cardiovascular outcomes trials (CVOTs) of once-weekly GLP-1 receptor agonists were identified.

SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER), and REWIND (dulaglutide) showed variations in trial design and patient characteristics.
CV safety of once-weekly GLP-1 receptor agonists was demonstrated compared to standard care.
Semaglutide and dulaglutide showed cardiovascular and renal benefits, while exenatide ER did not.
Four DPP-4 inhibitors demonstrated CV safety but lacked CV or renal benefits.
All three SGLT-2 inhibitors were associated with cardiovascular and renal benefits.

Simplified

WHAT IS KNOWN AND OBJECTIVE: People with type 2 diabetes (T2D) are at increased risk of cardiovascular disease (CVD), which in turn is associated with increased morbidity and mortality. The impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on cardiovascular (CV) outcomes has been investigated in CV outcomes trials (CVOTs). This review aims to help pharmacists and other healthcare professionals (HCPs) gain a better understanding of such CVOTs in T2D with a primary focus on the once-weekly (QW) GLP-1 RAs.

METHODS: This narrative review mainly focuses on the evaluation of the similarities and differences in the design and results of CVOTs involving currently approved and marketed QW GLP-1 RAs-semaglutide subcutaneous, exenatide extended-release (ER) and dulaglutide. Results from CVOTs of dipeptidyl peptidase-4 inhibitors (DPP4is) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are also included.

RESULTS AND DISCUSSION: Three CVOTs of QW GLP-1 RAs were identified for inclusion in this review: SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER) and REWIND (dulaglutide), all of which varied in terms of trial design, patient demographics and other baseline characteristics. Results from these CVOTs demonstrated the CV safety of QW GLP-1 RAs compared with standard of care. Additionally, CV and renal benefits were demonstrated for semaglutide and dulaglutide, but not for exenatide ER. The CV safety of four DPP4is and three SGLT2is was demonstrated. None of the DPP4is had a CV or renal benefit, whereas all three SGLT2is were associated with CV and renal benefits.

WHAT IS NEW AND CONCLUSION: This article provides an overview of the results from QW GLP-1 RA CVOTs, including the recently published results for dulaglutide, and places them within the broader T2D treatment landscape to help HCPs make informed decisions in daily practice. The QW GLP-1 RAs with benefits reaching beyond glycaemic control can provide a comprehensive treatment option for people with T2D at high risk of CVD, with CVD or chronic kidney disease.

Key numbers

26%

Risk Reduction of with Semaglutide

Compared to standard of care in SUSTAIN 6 trial.

12%

Risk Reduction of with Dulaglutide

Compared to standard of care in REWIND trial.

27,950

Total Participants in QW GLP-1 RA Trials

Combined enrollment from SUSTAIN 6, EXSCEL, and REWIND trials.

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Heart safety of once-weekly GLP-1 treatments in people with type 2 diabetes

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