The incidence of type 2 diabetes has increased over the last few decades in both adults and children. It is particularly prevalent in middle- and low-income countries (>25%), where mortality is four-times higher amongst those with vs those without diabetes. In middle-income countries, diabetes accounts for one-third of all deaths in adult patients. In more affluent countries, perhaps due to the increased uptake of cardiovascular protective medications, recent studies demonstrate a decline in all-cause mortality and the incidence of cardiovascular complications in patients with type 2 diabetes.
Insulin resistance at muscle, liver and adipose tissue, impaired insulin secretion and hyperglucagonaemia contribute to dysglycaemia in type 2 diabetes. Progress has been made in understanding the drivers of these metabolic phenotypes. Recent data highlights the notion that reduced peripheral adipose tissue storage capacity is a key determinant of the insulin-resistant state and that this link is mediated by specific and multiple genetic factors.
Weight loss is the cornerstone to type 2 diabetes management. The STAMPEDE trial reported that bariatric surgery plus intensive medical therapy was superior to the latter alone in improving glycaemic control, cardiovascular risk factors and quality of life after 5 years in moderate- and severely-obese patients with type 2 diabetes.
Almost a decade ago, the FDA mandated demonstration of cardiovascular safety with novel diabetes medications. Unexpectedly, many of these studies have demonstrated favourable effects on cardiovascular endpoints, with a series of landmark trials published in the last year. Recent evidence demonstrates that the SGLT2 inhibitors empagliflozin (EMPA-REG) and canagliflozin (CANVAS) reduce the risk of non-fatal myocardial infarction and cardiovascular death and slow the progression of diabetic kidney disease. Similarly, the GLP-1 receptor agonists liraglutide (LEADER) and semaglutide (SUSTAIN-6) have been shown to lower cardiovascular death and non-fatal events in patients with type 2 diabetes. Newer insulins, such as degludec, an ultra-long acting insulin, have recently been shown to be non-inferior to glargine in relation to cardiovascular events, but superior to glargine in regard to severe hypoglycaemia in type 2 diabetic patients with high cardiovascular risk (DEVOTE).