Victoza Reduces Risk of Cardiovascular Death, Heart Attack, and Stroke

What are the implications for other injected GLP-1 agonist drugs?

Novo Nordisk recently announced exciting highlight results from its clinical trial (called LEADER) on the once-daily injected GLP-1 agonist Victoza. The drug improves heart (or “cardiovascular”) safety in patients at high risk. Not only did Victoza decrease cardiovascular death for participants using it in the trial, but it also decreased the risk of non-fatal heart attacks (“myocardial infarction”) and non-fatal strokes. Full results from the trial will be presented at the ADA conference this summer.

Victoza is now the second diabetes drug to demonstrate it improves the heart in people with diabetes, following Lilly/BI’s Jardiance last year (an SGLT-2 inhibitor drug taken as a pill). The results come as a major and welcome surprise for Victoza, as the study was only designed to prove Victoza was safe and didn’t increase heart disease. At this stage, we don’t know how much it lowered risk – it will be exciting to find out in the summer.

Read on for our Q&A about GLP-1 agonists, the LEADER trial, and what these results mean for people with diabetes.

LEADER Q&A

How was the trial designed?

The trial enrolled 9,340 type 2 patients at high risk of cardiovascular disease (with either existing cardiovascular disease or multiple risk factors) and was designed to last for five years or until over 633 cardiovascular events (heart attack, stroke, or death) had taken place. Participants were randomized to either take Victoza or a placebo throughout the trial.

What caused the improvements to the heart?

According to Novo Nordisk’s Chief Medical Officer Mads Thomsen, the results were driven partly by better glucose control and partly by other factors, including improved weight, blood pressure, lipids, and inflammation.

How does Victoza compare to Jardiance in reducing heart disease?

We have to wait until this summer for the full data on Victoza to find out the magnitude of its risk reduction – did it reduce heart attacks by 5%? 10%? 25%? 50%? In a major positive, Victoza decreased cardiovascular death, non-fatal heart attacks, and non-fatal strokes; Jardiance, by contrast, only reduced cardiovascular death (by a remarkable 38%). Jardiance did not cut the risk of heart attacks or strokes. 

What does this mean for the GLP-1 agonist class?

Depending on the magnitude of the risk reduction, there is hope that the label on GLP-1 agonists could be improved to reflect their cardioprotective (“heart healthy”) benefits. That could encourage more insurance companies to cover them, more prescribers to recommend them, and more people with diabetes to use them.

Two more GLP-1 agonist trials, for Novo Nordisk’s injectable semaglutide and Intarcia’s implantable ITCA 650, are expected to report results this year. Results from these and other future trials could have massive implications for the entire GLP-1 drug class. There will be a full symposium at the ADA conference in June to discuss the LEADER results, and Novo Nordisk will submit the data to regulators in late 2016 for inclusion in the label.

What are GLP-1 agonists? (Byetta, Bydureon, Lyxumia, Tanzeum, Trulicity, Victoza)

GLP-1 is a hormone produced in the small intestine that stimulates insulin secretion and prevents glucagon secretion, thereby lowering blood sugar. It also acts to make you less hungry and to feel full faster. GLP-1 agonists are most often used by people with type 2 diabetes who have inadequate blood glucose control with just metformin and/or other oral drugs. They can be taken alone, or alongside metformin and/or other diabetes drugs. They work really well with insulin too. They have stronger efficacy than DPP-4 inhibitors but also increased side effects, particularly nausea. See more on GLP-1 agonists here. -NK