Diabetes drugliraglutide linked to lower risk of cardiovascular events in real world study

A large study using nationwide register data from Denmark and Sweden found that liraglutide, a drug for type 2 diabetes, was associated with reduced risk of major cardiovascular events. The study was published in The Lancet Diabetes & Endocrinology.

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The number of patients with type 2 diabetes is increasing rapidly in the world. Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes and interventions that reduce the burden of cardiovascular disease are therefore important.

“Liraglutide, a diabetes medication that became available for clinical use in 2009, is a glucagon-like peptide 1 receptor agonist that lowers blood sugar and reduces body weight. A large clinical trial published in 2016 also ignited much enthusiasm among patients and practitioners by showing that liraglutide reduced the risk of major cardiovascular events.” says principal investigator Björn Pasternak, senior researcher at Karolinska Institutet and affiliated with Statens Serum Institut.

Large cohort based on nationwide data from two countries

The current study was part of a collaboration between researchers at Karolinska Institutet in Sweden, Statens Serum Institut in Denmark, NTNU in Norway and the Swedish National Diabetes Register. The researchers used several nationwide registers with information on prescription drugs, diseases and other data from more than 46,000 patients in Denmark and Sweden from 2010 to 2016.

The researchers used a so called matched active comparator design, meaning that they compared around 23,000 patients initiating treatment with liraglutide with the same number of patients initiating treatment with another diabetes drug, DPP4 inhibitors. The main outcome in the study was major cardiovascular events, a composite outcome defined as myocardial infarction, stroke, or cardiovascular death. Other specific outcomes investigated, among others, were cardiovascular death and any-cause death.

Results indicate that liraglutide has cardiovascular effectiveness in routine clinical practice

The rate of major cardiovascular events was 14.0 per 1000 person-years among patients using liraglutide and 15.4 per 1000 among patients using DPP4 inhibitors, a statistically significant difference. The hazard ratio was 0.90 (0.83-0.98). In terms of absolute risk, this corresponded to 5 fewer major cardiovascular events per 1000 patients followed up for 3 years.

Use of liraglutide was also associated with reduced risk of cardiovascular death and any cause death. In a subgroup analysis where patients were divided into those who had previous major cardiovascular disease and those who did not, those with such history appeared to benefit most from treatment with liraglutide, although this was not a formally statistical significant difference.

“Overall, the results were largely consistent with those reported in the clinical cardiovascular outcome trial.” says Björn Pasternak.

“In a large-scale randomized clinical trial called LEADER, liraglutide was shown to significantly reduce the risk of major cardiovascular events among patients with established cardiovascular disease or who were at high cardiovascular risk.” says Mads Melbye, president and CEO of Statens Serum Institut.

”LEADER represents firm scientific evidence of this drug’s cardiovascular efficacy. However, there has been uncertainty whether the cardiovascular benefit translates to routine clinical practice, where broader unselected groups of patients are at different levels of baseline cardiovascular risk. Our study indicates that this is indeed the case and as such provides important confirmatory evidence from real-world clinical practice.”


Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden. Henrik Svanström, Peter Ueda, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak. The Lancet Diabetes & Endocrinology, online 5 December 2018, http://dx.doi.org/10.1016/S2213-8587(18)30320-6


Björn Pasternak, bjorn.pasternak@ki.se