The diabetes drug empagliflozin could cut the number of cardiovascular deaths by almost 40% as part of the treatment for type 2 diabetes, according to a study
published in New England Journal of Medicine on 17 September 2015.
Empagliflozin (Jardiance; Boehringer Ingelheim and Eli Lilly) acts by selectively inhibiting the sodium-glucose cotransporter 2 (SGLT-2), and so increasing glucose excretion in the blood. Type 2 diabetes is a major risk factor for cardiovascular disease, and patients who have both conditions have an increased death rate. As part of a company-sponsored phase III trial, 7,020 people with type 2 diabetes and established heart disease were given 10mg or 25mg of empagliflozin or placebo daily alongside their existing glucose-lowering therapy.
In those treated with empagliflozin, the risk of death from any cause was reduced by 32%, and the risk of death from cardiovascular causes was reduced by 38%. This included reductions in deaths from heart failure.
“This drug has the potential to be a game-changer in the treatment of diabetes, and it will be interesting to see whether it is a class effect, or is just seen in this drug,” says Partha Kar, consultant in diabetes and endocrinology at Portsmouth Hospitals NHS Trust. “These results in cardiovascular disease could drive a change to the guidelines, potentially moving empagliflozin earlier in the treatment paradigm.”
There have been questions about this class of drugs and risk of osteoporosis in the past, according to Kar, but the proportion of patients with bone fractures was low. Concerns have also been raised about the renal safety of the SGLT-2 inhibitors, but again, the rates of acute renal failure were low.
The only significant increase in side effects was a rise in the rate of genital infections, which is likely to be linked with the increased levels of urinary glucose. There was also a slight increase in the risk of stroke but this was not statistically significant.
“The effect on stroke will have to be monitored, and more studies will be needed,” says Kar. “However, as with any drug, it’s important to balance the benefits and the risks.”
The European Medicines Agency (EMA) approved empagliflozin in the European Union in May 2014, alone or in combination with other drugs. It is available in the UK and was recommended by the National Institute for Health and Care Excellence (NICE) in March 2015 as part of a dual or triple therapy for type 2 diabetes. According to Boehringer Ingelheim, it is the only glucose-lowering agent to have demonstrated cardiovascular risk reduction in a dedicated cardiovascular outcomes trial, and the researchers suggest that the study supports the use of empagliflozin in the long term.
“We welcome this additional evidence that empagliflozin can benefit people with type 2 diabetes,” says Douglas Twenefour, clinical adviser at Diabetes UK.
“However, it is important to highlight that all medication should be chosen on the basis of what is most appropriate for the individual patient and that the person with diabetes is involved in making the decision on which medication meets their needs.”