The TGA has approved an expanded indication for the blood glucose-lowering drug, empagliflozin (Jardiance, Boehringher Ingelheim, Eli Lilly) to protect against risk of cardiovascular death in patients with type 2 diabetes who also have established cardiovascular disease.
The cardioprotective indication – a first for any oral anti diabetic therapy – comes off the back of the US FDA’s approval late last year following its analysis of the drug’s mandatory regulatory outcome trial that was widely publicised in 2015 for revealing a surprising cardiovascular benefit in patients with type 2 diabetes at high CV risk.
The EMPA-REG Outcome trial showed that when combined with standard care the SGLT2 inhibitor reduced the risk for CV death by 38% compared with placebo.
Patients treated with empagliflozin also experienced a 32% reduction in all-cause mortality risk and a 35% reduction in risk for hospitalisation for heart failure despite many of the patients already being prescribed statins, ACE inhibitors or ARBs.
Sydney cardiologist and EMPA-REG investigator, Professor Andrew Sidone said the reduction in cardiovascular death seen with the empagliflozin rivals those recorded in early landmark cardiovascular trials.
He says that in diabetes, no drug has been shown to improve survival – at all.
“I tell people this is not a diabetes drug; this is a cardiovascular drug that just happens to lower blood glucose,” he told the limbic in an interview.
While its not yet known precisely how empagliflozin increases survival, Professor Sidone, who is currently involved in a number of studies to investigate just that, said patients in EMPA-REG who received the drug benefited from its effects much too early for any cardioprotective effect to be a result of the drug’s blood glucose lowering effect alone.
“Its actually really interesting, patients benefited super early – at around three months there was already a divergence [between the two groups] which continued over time; everything went in the right direction – CV mortality, hospitalisation for heart failure, people lost weight, blood pressure came down and heart rate fell.”
Importantly, he says, people were ‘peeing sugar’ one of the factors contributing to the drug’s weight loss effects and one that he says leads to an ‘escalation of benefit’.
“That seems to be the key here – most other diabetes medications either hide sugar, make you make less sugar or burn sugar faster whereas empagliflozin makes you put it in the toilet where it belongs.
“That’s important because it means that people lose weight … if you lose weight you’re more active. You’re capable of doing more things.”
Endocrinologist at Melbourne University and Austin Health, Associate Professor Richard O’Brien said that for doctors treating patients with diabetes and heart disease, it would be hard to overlook the cardiovascular benefits of a therapy when considering adding a blood glucose lowering agent to a patients drug regimen.
“Because coronary disease is so common in people with diabetes – more than 50% of people with diabetes will have or will develop coronary disease –physicians are going to have to look at the cardiovascular effects of the glucose lowering drugs … if you’ve got two drugs and one is going to have a cardiovascular benefit and there are no contraindications then obviously there’s going to be a preference for using that one,” he told the limbic.
But he also cautioned against ignoring conventional treatment.
“It’s most important that we are still rigorous with treating lipids, making sure that LDL cholesterols are at target and making sure we control blood pressure and other risk factors,” he said adding that translating the cardiovascular benefits of empagliflozin to a wider population would be difficult – particularly when the mechanism of action is not known.
“The data is very strong from the [EMPA-REG] trial but that is in people with pre existing coronary disease – that’s not to say the drug is inappropriate in Type 2 diabetics without CVD – it’s a drug which is good for lowering blood glucose, it reduces weight and physicians will use it quite widely from that point of view.
But if we’re talking specifically about reducing CVD, I think for the moment we can only say that we know that’s the case in people with existing CVD and we really need to wait for more studies in this drug class in people without coronary disease before generalising that benefit to the wider diabetic population.”