An exciting new class of medicine for people with type 2 diabetes, which cuts their risk of heart failure and death, is now available in Singapore.
New users of these drugs can see a reduction in hospitalisation for heart failure and death from any cause, compared to other glucose loweringdrugs for type 2 diabetes.
This was the discovery of a large international study from 2012 to 2016, published in early 2017.
Researchers looked at data from more than 300,000 patients with type 2 diabetes, from the United States and five European countries, most of whom did not have established cardiovascular disease. They were followed up for around a year.
It was found that the drugs reduced rates of hospitalisation for heart failure by 39 per cent, and death from any cause by 51 per cent, compared to other types of oral medication for diabetes.
The drugs studied were sodium glucose transporter 2 (SGLT2) inhibitors, which remove glucose via the kidneys. They comprise dapagliflozin, canagliflozin and empagliflozin, which have all been approved for managing type 2 diabetes in Singapore since 2014.
Associate Prof Tan Ru San, Senior Consultant, Department of Cardiology, National Heart Centre Singapore (NHCS), described the results as exciting, and said such a positive outcome is greatly relevant to Singapore, where there is now a war on diabetes.
“Diabetes and heart failure are intricately linked,” said Prof Tan, who is also Adjunct Associate Professor of Duke- NUS Medical School.
He said diabetes – a condition where there is high blood sugar level – causes complex changes in the body through inflammation and stress. This can lead to diseases of the blood vessels, an increased risk of blood clotting, scarring and cell death. If heart structure and function are adversely affected, it can cause heart failure.
“These drugs have a unique mechanism of action that removes excess sugar in the urine from the body of diabetic patients. They are a significant advancement for safe oral treatment of diabetes and are even beneficial for reducing the risks of cardiovascular events and heart failure in patients with type 2 diabetes.”
Backed by the study results, Prof Tan said he would confidently use them on patients with poorly controlled type 2 diabetes, and tell them they may also see a reduction in their risk of heart failure.
Prescription and subsidies
Since May 3, 2017, the Agency for Care Effectiveness has recommended dapaglif lozin be included in the Medication Assistance Fund (MAF).
This means that type 2 diabetes patients – whose diabetic control remain poor despite the use of standard medication, or for whom standard medication cannot be safely used, and who are eligible for MAF assistance – can now have access to and receive government support for dapagliflozin to help control their condition.
Patients on dapaglif lozin are prescribed one tablet a day, with polyclinics and restructured hospitals pricing it at $1.36 per 10mg tablet.
With the MAF subsidy, the price can bereduced by 50 per cent or 75 per cent.
“Although the drugs [SGLT2 inhibitors] are not approved for heart failure treatment per se, I hope that the increased access to them can help patients with diabetes, especially those with complications of heart failure,” he said.
The standard drug prescribed as the first choice is metformin, said Prof Tan. “If the control is not good, we can immediately begin combination therapy. In cases where metformin or the usual drug combinations do not work, a drug like an SGLT2 inhibitor would be a very reasonable choice.”
An SGLT2 inhibitor may also be prescribed when a patient is unable to tolerate side effects of the other more traditional type 2 diabetes drugs. These can only be prescribed for patients with reasonable kidney function. And as these drugs increase urinary sugar excretion, they can raise the risk of urinary tract or genital tract infections.
As users lose sugar and fluids, some patients who are new users of SGLT2 inhibitors may have low blood pressure and feel a bit faint, so it takes a period of acclimatisation, Prof Tan said. On the other hand, the sugar loss can prevent weight gain or may even help people lose weight.
Diabetes and heart failure in Singapore
The rate of diabetes in Southeast Asia, including Singapore, is more alarming than in the West, due to factors such as a carbohydrate-rich diet, a sedentary lifestyle and smoking, said Prof Tan Ru San.
Asian patients also suffer more complications from it. “They develop heart failure earlier, and our patients do not do as well, for various reasons.”
Unlike in the West, where the incidence of heart attacks is coming down, it is still rising in Singapore, he said. “We have not managed to control all the risk factors effectively.”
Between 2008 and 2015, NHCS admitted about 500 diabetic persons for heart failure annually, with around 2 per cent of them dying during their hospital stay.
Meanwhile, the incidence of diabetes in Singapore itself is set to rise. Based on estimates by the Saw Swee Hock School of Public Health, numbers could reach 670,000 by 2030 and nearly one million by 2050.
Globally, it can grow from more than 400 million adults worldwide now to more than 600 million by 2040.