Underuse of GLP-1 receptor agonists in the management of type 2 diabetes despite a favorable benefit-safety profile

ABSTRACT

Introduction

Patients with type 2 diabetes (T2DM) are at high risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular death. Cardiovascular protection is a key objective in T2DM.

Areas covered

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their efficacy in reducing major cardiovascular events in high-risk patients with T2DM in placebo-controlled trials, a finding confirmed in observational studies compared with other glucose-lowering agents. Overall, GLP-1RAs have a good safety profile associated with a favorable benefit/risk ratio for the management of T2DM, even if their cost-effectiveness might be questionable. International guidelines recommend GLP-1RAs as preferred glucose-lowering agents in patients with ASCVD and as a valuable alternative in overweight/obese patients with T2DM. However, real-life studies worldwide revealed that only a minority of patients receive a GLP-1RA, despite a positive trend for increased prescriptions in recent years. Surprisingly, however, fewer patients with established ASCVD are treated with these cardioprotective antihyperglycemic agents versus patients without ASCVD.

Expert opinion

The reasons for GLP-1RA underuse in clinical practice are multiple. Multifaceted and coordinated interventions targeting all actors of the health-care system must be implemented to stimulate the adoption of GLP-1RAs as part of routine cardiovascular care among patients with T2DM, especially in those with ASCVD.

Plain Language Summary

Patients with type 2 diabetes are at high risk of atherosclerotic cardiovascular disease, especially myocardial infarction and ischemic stroke. Cardiovascular protection should be considered as a key objective when treating those patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), an injectable therapy for the treatment of hyperglycemia, have proven their efficacy in reducing major cardiovascular events (cardiovascular mortality, myocardial infarction, ischemic stroke) both in controlled trials compared to placebo and in real-life studies compared with other glucose-lowering agents. These consistent findings profoundly influence international guidelines which recommend GLP-1RAs as preferred glucose-lowering agents in patients with atherosclerotic cardiovascular disease or at high risk of developing this complication. However, real-life studies worldwide revealed that only a minority of patients receive a GLP-1RA. An even more surprising finding was that GLP-1RAs are less prescribed in patients with established atherosclerotic cardiovascular disease, including antecedents of coronary heart disease and cerebrovascular disease, than in patients without such cardiovascular complications. The reasons for GLP-1RA underuse in clinical practice are multiple and concern physicians, patients, and health-care system. Bridging the gap between evidence-based cardiovascular protection with GLP-1RAs and their underuse in daily clinical practice in patients with type 2 diabetes at high risk is crucial from a public health viewpoint.

KEYWORDS:

• Atherosclerotic cardiovascular disease
• cardiovascular outcome trial
• GLP-1 receptor agonist
• observational studies
• real-world clinical practice

Article highlights

• Atherosclerotic cardiovascular disease (ASCVD) is a common and major complication associated with type 2 diabetes (T2DM).

• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events (MACEs) in placebo-controlled cardiovascular outcome trials.

• The cardiovascular protection of GLP-1RAs has been confirmed in real-life retrospective observational studies compared with other glucose-lowering agents (except gliflozins).

• The safety profile of GLP-1RAs is reassuring and this pharmacological class has a good benefit–risk ratio, yet the cost-effectiveness is more debatable because of a higher drug price.

• Despite the recommendations of international guidelines, the use of GLP-1RAs remains rather low in clinical practice (even if a positive trend was present in recent years) and surprisingly even lower in patients with T2DM and ASCVD.

• Bridging the gap between evidence-based cardiovascular protection and real-life GLP-1RA underuse in patients with T2DM at high cardiovascular risk is crucial from a public health viewpoint.

Declaration of interest

A Scheen has received lecturer/scientific advisor/clinical investigator fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, NovoNordisk and Sanofi. He worked as clinical investigator in EMPA-REG OUTCOME, CANVAS-R, DECLARE-TIMI 58, LEADER and HARMONY Outcomes cardiovascular outcome trials. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.