Over the relatively short time since their launch, the use of DPP 4 inhibitors has accelerated to the point that they are widely used in the treatment of Type 2 diabetes, often being used early in the treatment pathway. This is despite the lack of significant evidence about their cardiovascular impact and the fact that the diabetes world has only just digested the impact of the Rosiglitazone debacle. This lead to new FDA guidelines regarding the development of new drugs for diabetes and their being subjected to CV risk studies.
The recent publication of 2 studies, SAVOR-TIMI 53 and EXAMINE have reassuringly demonstrated the relative safety of two DPP 4 inhibitors (Saxagliptin and alogliptin) in terms of cardiovascular risk. In SAVOR-TIMI 53, 16492 patients with Type 2 diabetes and established cardiovascular disease or multiple risk factors received either Saxagliptin or placebo. There was no significant difference between the groups in the primary end point – a composite of CV death, ischaemic stroke or myocardial infarction. However, there was an increased incidence of heart failure in the Saxagliptin group, a finding requiring further investigation. Unsurprisingly, the HbA1c Saxagliptin group was significantly lower.
In the EXAMINE study of 5380 patients with Type 2 diabetes and recent myocardial infarction or unstable angina (i.e. high risk), there was no significant difference in a similar primary end point in those patients treated with Alogliptin compared to standard care. AS with SAVOR-TIMI 53, HbA1c was lower in the Alogliptin group.
So, good news, the widespread uptake of these two DPP 4 inhibitors at least does not seem to increase cardiovascular risk. Other studies into agents in this class are also awaited. However, one disappointment is that there was no evidence that improving glycaemic control with these agents impacted on CV risk – although the length of the studies probably precluded this. Both studies also failed to show any benefit on other endpoints such as renal impairment, weight gain or hypoglycaemia.
So, for the health care professional looking after patients with Type 2 diabetes, no sudden change in oral hypoglycaemic prescribing is required but when it comes to cardiovascular risk reduction, the optimal approach should continue to revolve around aggressive treatment of CV risk factors rather than intensive glycaemic control.
Dr Mark Freeman