Cardiovascular safety of liraglutide for the treatment of type 2 diabetes

ABSTRACT

Introduction: Liraglutide is a GLP-1 RA that is an option for treatment of T2DM. Typical of all new glucose-lowering agents, its CV safety profile is of great interest.

Areas covered: This article outlines the efficacy of the GLP-1 RA liraglutide from RCTs, moving through the pivotal phase 3 LEAD trials, and subsequent meta-analyses to assess CV safety. This review describes evolution of regulatory requirements to obtain safety information through dedicated CVOTs.

Expert opinion: Since the FDA mandated that CV outcomes for new diabetes therapies should be assessed via a dedicated CVOT, opinion of their utility in T2DM evolved from cynicism through to enthusiasm. In LEADER, liraglutide became the second modern glucose-lowering agent to demonstrate significant CV benefit. CVOTs are now providing important answers, highlighting the CV benefits of modern glucose-lowering agents, but also raising several questions, notably whether the effects seen with liraglutide and empagliflozin are class-effects or are unique to these molecules. Furthermore it is unknown if these results in patients with high CV risk are applicable to all patients with T2DM, and should be incorporated into new treatment guidelines. In our view it’s prudent to suggest that CVOT findings cannot currently be extrapolated to the whole T2DM population.

KEYWORDS:

• Type 2 diabetes
• liraglutide
• LEADER
• safety

Declaration of interest

R Chudleigh has attended advisory boards, received travel grants and speaker fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, MSD, Novo Nordisk, Sanofi Aventis & Takeda. S Bain receives consulting fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Sanofi Aventis, and Merck Sharp & Dohme, and grant support from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Sanofi Aventis, Merck Sharp & Dohme, GenMedica, and CeQur. Writing assistance was utilized in the production of this manuscript provided by Nathan Ley, PhD, of Watermeadow Medical, an Ashfield Company, part of UDG Healthcare plc and funded by Novo Nordisk A/S. The authors have 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.

Additional information

Funding

This paper was funded by Novo Nordisk in the form of writing assistance.