Diabetes-CV Disease Link Boosts EASD Buzz
Executive Summary
Linkage between cardiovascular disease and type 2 diabetes was a top theme of discussion and data presented at this year's EASD meeting in Portugal's capital.
Rising evidence that severe low blood sugar levels raise the risk of type 2 diabetes patients dying from heart attacks and research into therapies addressing that link dominated this year's meeting of the European Association for the Study of Diabetes (EASD).
More than 15,000 delegates from over 130 countries attended the meeting in Lisbon, Portugal, where the scientific program included more than 1,200 talks and presentations on the latest results in diabetes research by leading experts in the field.
But delegates said the chief overall takeaway from the five-day event, which ended Sept 15, was the rising evidence of the interrelationship of cardiovascular disease (CV) and severe hypoglycemia.
"I've been to 25 EASD and 25 ADA (American Diabetes Association) meetings since 1993, and at long last we can declare victory and show that our research is improving heart outcomes. Diabetes is one of the top five killers in the world … We can now start doing something about that," said Mads Krogsgaard Thomsen, Novo Nordisk AS 's chief science officer.
“Individuals who have experienced more hypos through their life will also experience faster heart attacks. This should help create more awareness of diabetes and its dangers.” – Mike Doustdar, head of international operations, Novo Nordisk
His company's head of international operations Maziar Mike Doustdar summarized by saying that "what's happening more and more at these meetings like EASD and ADA is that we see cardiometabolic syndromes are more and more interlinked. It's almost hard to find a patient today who is taking insulin but who is not taking a lipid-lowering statin, or a hypertension drug. Or who has not been to a cardiologist once a year – or also obese, if they have type 2 diabetes."
Novo Nordisk's DEVOTE
Doustdar and Thomsen spoke separately to Scrip at the annual EASD gathering as the Danish diabetes drug maker released new analyses from its DEVOTE trial, showing that people with type 2 diabetes who experience severe hypoglycemia are at greater risk of death. DEVOTE showed Novo Nordisk’s Tresiba (insulin degludec) reduced the rate of severe hypoglycemia by 40% and the rate of nocturnal severe hypoglycemia by 53% compared to insulin glargine U100 in people with type 2 diabetes.
CSO Thomsen told Scrip the DEVOTE trial means that "now we can start linking the risk of dying in the next fortnight if you've had severe hypoglycemia. What is that risk? According to DEVOTE, it's 12 times higher than if you have not had that happen to you. And if the time frame is within one year, then the risk is three times higher that you'll die than if you didn't have an episode within that time. This doesn't say that we're proving that severe hypo precipitates death or cardiovascular attacks, but there's certainly a link," Thomsen said in an interview.
Taking Heart At EASD
Commenting on the increased CV focus in the field, Elisabeth Björk, who heads AstraZeneca PLC's cardiovascular and metabolic diseases (CVMD) development unit, said: "for many years, diabetes research and clinical practice around diabetes has been very glucose-centric. It's been focusing on glucose and HbA1c and what its importance is and the different treatments around that. The movement right now is towards analyzing what the impact is on the cardiovascular and renal part and the interconnection between the diabetes perceived and the kidney and the heart."
The field of diabetes therapeutics is now involving data in research about cardiovascular effects of different drugs and different drug classes that don't just address the glucose part of the HbA1c but also the effects of cardiovascular mortality and renal health. "That is why you're not only seeing endocrinologists and physicians in that field here at EADS but also more cardiologists and renal experts. They are all working together, while putting the patients in the center to try and piece together a total picture," she told Scrip.
Ludovic Helfgott, AstraZeneca's global vice-president for the CVMD business, told Scrip the diabetes research community "has now an added layer of scientific focus, that being cardiovascular benefits."
AstraZeneca used the EASD congress to release full results of its EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial. It showed cardiovascular safety with Bydureon (exenatide extended-release) in patients with type 2 diabetes at a wide range of CV risk.
"What we have done with the EXSCEL study – the biggest ever done with a GLP-1 analog therapy with 14,500 patients taking part – is we've proved that once-weekly exenatide is truly safe from a cardiovascular perspective in a broad patient population," said Björk.
There were also fewer CV events observed in the exenatide arm of the EXSCEL trial, with 839 or 11.4% observed versus 905, equating to 12.2%, although the primary efficacy objective of a superior reduction in a composite measure of major adverse CV events (MACE) narrowly missed statistical significance (p=0.061). Headline results from the six-year trial were released in May. Also, patients on exenatide had a 14% lower incidence of death than those in the placebo arm, she noted.
CV Risk May Boost Diabetes Awareness
Novo Nordisk's Doustdar said diabetic patients have hitherto not fully appreciated the urgency to treat their condition consistently. The related association of cardiovascular disease may help change that, to the benefit of diabetic patients. He used multiple sclerosis as an example.
"MS, like type 1 diabetes, is an autoimmune disease. When people discover they have it, they know it won't kill them immediately but it can put them in a wheelchair, there's a chance of losing your balance, or your speech, and so on. The fear of that means the patient runs to the doctor as soon as they have seen the first symptoms of MS … compare that to the reaction of type 2 diabetes patients. We have long shown that type 2 diabetes can end up with amputations, kidney failure, blindness before death earlier than planned, but still patients and doctors seem not to have shown the requisite urgency to get or give treatment."
That will hopefully change now that more physicians are coming to the conclusion that severe hypoglycemia episodes result in cardiovascular risks. "So, individuals who have experienced more hypos through their life will also experience faster heart attacks. This should help create more awareness of diabetes and its dangers than we have previously been able to do."
Summing up, Doustdar said that "if there's one big theme that will change the diabetes landscape over the next decade, I think, it is the special connectivity between CV and type 2 diabetes."