Drugs for diabetes: the cardiovascular evidence base

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Cardiovascular (CV) disease is a cause of significant morbidity and mortality in patients with type 2 diabetes. While lowering glucose levels is central to the management of diabetes, the relationship between glycaemia and CV disease is not straightforward, with both hyper- and hypoglycaemia contributing to vascular risk. Moreover, the type of hypoglycaemic agent may determine predisposition to CV events, adding another layer of complexity to patient management.

Over the past decade, newer hypoglycaemic therapies have been forced to undergo rigorous randomised-controlled trials (RCTs) to confirm vascular non-inferiority and investigate possible superiority. This has provided an unprecedented wealth of data and demonstrated that inhibitors of dipeptidyl peptidase are CV neutral, whereas agents in the sodium-glucose co-transporter family offer CV protection and reduce heart failure risk. Some glucagon-like peptide-1 analogues have also shown vascular protection. In contrast to newer agents, metformin and agents in the sulfonylurea (SU) group have not been investigated in high-quality RCTs. Current evidence, derived from meta-analyses and observational studies, suggests that metformin is either CV neutral or offers vascular protection in some patients, yet to be fully characterised. SUs, on the other hand, may increase vascular risk, although concrete evidence for this is lacking. Interestingly, agents in the same class may have different vascular effects, as has been the case with rosiglitazone and pioglitazone, creating difficulties with guidelines and treatment recommendations.

Ongoing and future RCTs, together with appropriate mechanistic studies, will further help to optimise hypoglycaemic therapy to maximise vascular benefits in patients with diabetes.

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