Results of recent cardiovascular outcome studies have shown significant reductions in cardiovascular disease and overall mortality using sodium–glucose cotransporter-2 inhibitors and glucagon- like peptide-1 receptor agonists and have made us rethink our choices of pharmacotherapy. These agents should now be considered earlier in the management of patients with type 2 diabetes to reduce cardiovascular risk, particularly in those with existing cardiovascular disease.
- Type 2 diabetes is associated with a significant increase in cardiovascular risk.
- Early glycaemic control reduces microvascular complications that in the long term may also translate to decreased macrovascular complications.
- Traditional antihyperglycaemic agents do not appear to have any specific beneficial cardiovascular effects, with the possible exception of metformin.
- More recently, some trials have shown significant reductions in cardiovascular and overall mortality using sodium–glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists in specific patient populations, particularly in those with established cardiovascular disease.
- SGLT-2 inhibitors may also reduce hospitalisation with heart failure.
- These agents should now be considered earlier in the management of patients with type 2 diabetes to reduce cardiovascular risk, particularly in those with existing cardiovascular disease.
- Management of each patient should be individualised; if these newer agents are used, the relative benefits and potential side effects should always be discussed with the patient.
Picture credit: © milatas/stock.adobe.com Model used for illustrative purposes only
The prevalence of type 2 diabetes continues to rise because of a combination of factors, particularly the ever increasing rate of obesity, but also longer life expectancy and increased vigilance in screening and detection. It has been well established that type 2 diabetes is associated with an increase in premature cardiovascular complications and mortality. Traditional antihyperglycaemic agents have had no clear impact on decreasing cardiovascular risk, but early glycaemic control lowers the rate of cardiovascular mortality in the long term.1,2
Newer therapies, namely the sodium–glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, address some of the complex pathophysiological abnormalities associated with diabetes and have lower rates of hypoglycaemia and weight gain. In recent cardiovascular outcome studies, these two drug classes have also shown beneficial cardiovascular effects, including reductions in cardiovascular death in patients with established cardiovascular disease taking empagliflozin and patients at high risk of cardiovascular disease taking liraglutide.3,4
One of the goals in the management of diabetes must be to reduce diabetes-related death and macrovascular and microvascular complications. Management entails much more than just lowering blood glucose levels and cannot focus solely on glycaemic control. A multifactorial approach toward lowering cardiovascular risk is essential and should include targets such as lipid levels and blood pressure. This multifactorial approach has been shown to have significant benefits.5
More recently, the results of cardiovascular outcome studies evaluating the safety of the newer pharmacological agents have expanded the focus of management to include the potential beneficial nonglycaemic effects of these agents.3,4 This article focuses on the effects of antihyperglycaemic medications on cardiovascular disease; however, this focus in no way discounts the profound effects of diabetes on microvascular and other complications.
Epidemiology of diabetes and cardiovascular disease
A global problem
About 387 million people worldwide, or 8.3% of adults, have type 2 diabetes.6 By 2035 about 592 million people, or one in 10 adults, will have type 2 diabetes.6 In 2014, type 2 diabetes led to the deaths of about 4.9 million people, which equates to a person dying from type 2 diabetes-related conditions every seven seconds.6 Globally, type 2 diabetes is associated with a 1.76-fold relative increased risk of death from cardiovascular disease and a 2.26-fold increased risk of stroke.7
An Australian problem
In Australia, cardiovascular disease is estimated to account for more than 80% of deaths in people with type 2 diabetes.8 On average, a 60-year-old of either sex with type 2 diabetes but no history of cardiovascular disease would die about six years younger than their counterpart without type 2 diabetes. A 60-year-old of either sex with both type 2 diabetes and a history of cardiovascular disease would die about 12 years earlier than someone without either condition.9,10